WNK1-a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) contro... more WNK1-a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control-is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23-4.9), DBP 1.9 mmHg (95%CI:0.7-3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0-1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7610 23 , combined with BRIGHT data-set p = 2610 24 , n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p,10 27). We identified several common haplotypes to be associated with increased BP and multiple low frequency haplotypes significantly associated with lower BP (.10 mmHg reduction) and risk for hypertension (OR,0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH.
The median is denoted as the line that bisects the boxes. The whiskers are lines extending from e... more The median is denoted as the line that bisects the boxes. The whiskers are lines extending from each end of the box covering the extent of the data on 1.5 × interquartile range. Circles represent the outlier values. P-values from Mann-Whitney U-test are shown, applied to test the statistical difference in the distributions of SBP or GFR estimates between two groups.<b>Copyright information:</b>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"http://www.biomedcentral.com/1471-2350/9/25BMC Medical Genetics 2008;9():25-25.Published online 10 Apr 2008PMCID:PMC2330028.
<b>Copyright information:</b>Taken from ", a positional candidate for blood pres... more <b>Copyright information:</b>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"http://www.biomedcentral.com/1471-2350/9/25BMC Medical Genetics 2008;9():25-25.Published online 10 Apr 2008PMCID:PMC2330028.
Singleton polymorphisms were excluded from calculations.<b>Copyright information:</b>... more Singleton polymorphisms were excluded from calculations.<b>Copyright information:</b>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"http://www.biomedcentral.com/1471-2350/9/25BMC Medical Genetics 2008;9():25-25.Published online 10 Apr 2008PMCID:PMC2330028.
Purpose. beach handball is a physically demanding sport. the aim of the study was to establish th... more Purpose. beach handball is a physically demanding sport. the aim of the study was to establish the relationships between anthropometric characteristics and overarm ball speed, a key performance factor. Methods. Overall, 11 male players from the Spanish beach handball national team were recruited. throw speed was assessed in 3 throw types: standing throw (St), standing throw after two steps (rSt), and jump throw with a run-up and self-spin (rSSt). Pearson correlation was used to determine the correlation between variables. Magnitudes were evaluated qualitatively with magnitude-based inference, and the effects of anthropometric variables on the throw tests were analysed with stepwise multiple regression. Results. Maximal throw speed was 25.64 ± 4.14 m • s-1 for St, 23.71 ± 4.24 m • s-1 for rSt, and 24.83 ± 5.49 m • s-1 for rSSt. Large positive correlations were found between throw speed and middle, ring, and little finger lengths (P4 polygon) (r = 0.66 and 0.61 for St and rSSt, respectively). Very large (r = 0.77) and large (r = 0.68) correlations were observed between St and rSt, respectively, and elbow breadth. these results were likely positive for St: P4 (76/24/0), elbow epicondyle distance (EED) (91/9/0); and for rSt: EED (79/21/0); and possibly positive for rSt: P4 (68/32/0). St and rSt were predicted by P4 in 44% and by combining P4 and finger span FS1 in 68%. Conclusions. St and rSt ball speed in beach handball was related to specific hand/elbow anthropometric characteristics which can be easily measured.
The aims of this study were 1. to fix main sexual maturation signs and anthropometric measurement... more The aims of this study were 1. to fix main sexual maturation signs and anthropometric measurements, and 2. to investigate relations between maturational status and main anthropometric parameters (i.e. skinfolds, girths, lengths, breadths/lengths) in 12-15-year old boys. In total, 361 boys from Tartu, Estonia, were studied. Body height and weight, 9 skinfolds, 13 girths, 8 lengths and 8 breadths/lengths were measured. Pubertal stages were determined according to the criteria described by Tanner (1962). Self-assessment of pubic hair (PH1-PH5) was used. Genital development (G1-G5) was estimated by palpating the left testis and matching the size of wood ovoid of the Prader orchidometer. Finally, boys were asked about oigarche (= age at the first ejaculation of sperm). Most of the measured anthropometric variables were significantly different in boys of different chronological age and sexual maturity groups. By linear discriminant analysis, the safety of separation of the chronological age groups was higher than by sexual maturation variables. Nonlinear discriminant analysis allowed to separate sexual maturity groups by anthropometric variables up to 99% security. It was concluded that though the growth and development of a child is highly individual, on an average the anthropometric characteristics alter very constantly with the increase of age and biological maturation. Our results indicated that there were some significant differences in the anthropometrical parameters depending on the chronological age and biological maturation. Mostly length and breadth/length parameters change during the studied age period in respect to sexual development subgroups of boys. The skinfold thicknesses were not changed or even decreased.
The outcome of Genome-Wide Association Studies (GWAS) has challenged the field of blood pressure ... more The outcome of Genome-Wide Association Studies (GWAS) has challenged the field of blood pressure (BP) genetics as previous candidate genes have not been among the top loci in these scans. We used Affymetrix 500K genotyping data of KORA S3 cohort (n = 1,644; Southern-Germany) to address (i) SNP coverage in 160 BP candidate genes; (ii) the evidence for associations with BP traits in genome-wide and replication data, and haplotype analysis. In total, 160 gene regions (genic region610 kb) covered 2,411 SNPs across 11.4 Mb. Marker densities in genes varied from 0 (n = 11) to 0.6 SNPs/kb. On average 52.5% of the HAPMAP SNPs per gene were captured. No evidence for association with BP was obtained for 1,449 tested SNPs. Considerable associations (P,10 23) were detected for the genes, where .50% of HAPMAP SNPs were tagged. In general, genes with higher marker density (.0.2 SNPs/kb) revealed a better chance to reach close to significance associations. Although, none of the detected P-values remained significant after Bonferroni correction (P,0.05/2319, P,2.15610 25), the strength of some detected associations was close to this level: rs10889553 (LEPR) and systolic BP (SBP) (P = 4.5610 25) as well as rs10954174 (LEP) and diastolic BP (DBP) (P = 5.20610 25). In total, 12 markers in 7 genes (ADRA2A, LEP, LEPR, PTGER3, SLC2A1, SLC4A2, SLC8A1) revealed considerable association (P,10 23) either with SBP, DBP, and/or hypertension (HYP). None of these were confirmed in replication samples (KORA S4, HYPEST, BRIGHT). However, supportive evidence for the association of rs10889553 (LEPR) and rs11195419 (ADRA2A) with BP was obtained in meta-analysis across samples stratified either by body mass index, smoking or alcohol consumption. Haplotype analysis highlighted LEPR and PTGER3. In conclusion, the lack of associations in BP candidate genes may be attributed to inadequate marker coverage on the genome-wide arrays, small phenotypic effects of the loci and/or complex interaction with lifestyle and metabolic parameters.
Site/WebVersion.aspx). Determination of genotypes and alleles of rs4343 and rs4291 polymorphisms ... more Site/WebVersion.aspx). Determination of genotypes and alleles of rs4343 and rs4291 polymorphisms of ACE gene was performed at discharge using "iCycler iQ" detection system (BIO-RAD, USA) by TaqMan-assays. Additional exclusion criteria were clinically significant comorbidities. In 36 months after the index event a telephone contact was made with the patients or their relatives to identify the endpoints. We succeeded to specify a patient's status "dead or alive" in 96.6% of cases. In NSTE-ACS and STE-ACS a mortality from any causes was 12.9% (n=22) and 9.9% (n=17) correspondingly, cardiovascular mortality -9.4% (n=16) and 9.4% (n=16) and the incidence of endpoints "cardiovascular death/nonfatal myocardial infarction" -12.8% (n=21) and 15.8% (n=27). Results: A combination of TT genotype of rs4291 polymorphism and GG genotype of rs4343 polymorphism of ACE gene was conclusively associated with three-year total mortality both in STEMI (p=0.02) and in NSTEMI (p<0,0001). However, a statistically significant relationship of these genotypes with cardiovascular mortality as well as the risk of death/nonfatal MI was revealed only in NSTEMI. The ROC-curves analysis showed that in NSTEMI a combined use of GRACE score with rs4291 and rs4343 polymorphisms had significantly (p<0.0001) increased its predictive capability in regard to all previously described endpoints. Thus, the values of the area under ROC-curves in prognosis of total mortality were 0.71 (0.58-0.85) and 0.81 (0.70-0.92) for GRACE and GRACE+ACE scores correspondingly, in prognosis of cardiovascular mortality -0.66 (0.46-0.87) and 0.91 (0.82-0.99) and in prognosis of cardiovascular mortality/nonfatal MI -0.68 (0.55-0.81) and 0.79 (0.68-0.89). As concerns the STE-ACS a significant (p=0.001) improvement of prognostic value of GRACE score supplemented by the identification of rs4291 and rs4343 polymorphisms was obtained only for total mortality within three years. Thus, the values of the area under ROC-curves for GRACE score and the own model (GRACE+ACE) were 0.72 (0.62-0.82) and 0.77 (0.66-0.87 correspondingly. Conclusion: Modification of GRACE 2.0 score by adding the data on the genotypes of rs4291 and rs4343 polymorphisms of ACE gene more effectively improves the mortality prediction within three years after NSTEMI than after STEMI.
On 15 October 2022, 125 years passed from the birth of Juhan Aul (1897-1994), the founder of Esto... more On 15 October 2022, 125 years passed from the birth of Juhan Aul (1897-1994), the founder of Estonian anthropology. The article gives a brief overview of the versatile scientist's contribution to the history of science and anthropology. Some aspects that have been particularly emphasized in his works, presentations and manuscripts and the importance of the anthropological data throughout the ages are highlighted. As a further development of the data collected by Juhan Aul, Markus Valge's doctoral thesis was published in the year of his 125 th birthday.
The aim of the study was to create an anthropometric model that would correlate bodily characteri... more The aim of the study was to create an anthropometric model that would correlate bodily characteristics with nutritional variables. In 131 female students (aged 17–23 years), 32 body measurements and 11 skinfolds were measured and 6 body composition characteristics calculated. In the nutrition study, 24-hour menus were used, where the content of energy and main nutrients – proteins, fats and carbohydrates – was found. The amount of food consumed correlated positively with body density and negatively with weight, circumferences, skinfolds and all indicators of body fat content (r = 0.17 – 0.31). To describe the body as a whole, a 5 SD classification was used with the following body types: (1) small weight, small height; (2) medium weight, medium height; (3) big weight, big height; (4) pycnomorphs (big weight, small height) and (5) leptomorphs (small weight, big height). Food consumption per 1 kg of body weight differed between classes, being relatively high in the class of small subjects and decreasing gradually in the medium and big class. Leptomorphs had significantly higher consumption of energy, fats and carbohydrates compared to pycnics. Consequently, different body measurements can be used to characterize body build, but to characterize the body as a whole, a height-weight classification is needed.
Background: Kidneys have an important function in blood pressure (BP) regulation and elevated BP ... more Background: Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, N-acetyltransferase 8 (NAT8) expressed in embryonic and adult kidney and associated with nephrotoxicity response. Methods/Results: We report the first study exploring NAT8 as a potential candidate gene for blood pressure and kidney function. The resequencing (n = 42, random Estonian samples) identified 15 NAT8 polymorphisms, including 6 novel variants. The diversity of NAT8 5' upstream region (Ï€/ bp = 0.00320) exceeded up to 10 times the variation in the NAT8 genic region (Ï€/bp = 0.00037) as well as the average variation (Ï€/bp = 0.00040) for the promoters of 29 reference genes associated with hypertension. We suggest that a potential source for such high variation could be an active gene conversion process from NAT8B duplicate gene to NAT8. Similarly to NAT8, several reference genes with the most variable upstream regions have also duplicate copies. The NAT8 promoter SNPs were targeted with pilot quantitative association studies for blood pressure (n = 137, healthy unrelated individuals) and for the index of kidney function-estimated glomerular filtration rate (eGFR; n = 157 hypertensives with and without nephropathy). Minor alleles of these polymorphisms revealed a significant protective effect against elevated systolic BP as well as kidney failure in hypertension patients (p < 0.05; linear regression model, addictive effect). Conclusion: The full resequencing and pilot association study of a novel positional candidate gene for blood pressure and renal function, human N-acetyltransferase 8, suggested a contribution of highly variable NAT8 promoter polymorphisms in determination of systolic blood pressure and eGFR. Based on in silico analysis, we raise the hypothesis that the alternative SNP alleles of the NAT8 upstream region may have differential effect on gene expression.
Bivariate body height-weight classification-a useful tool in systematization and analysis of medi... more Bivariate body height-weight classification-a useful tool in systematization and analysis of medical data 27 Bivariate body height-weight classification-a useful tool in systematization and analysis of medical data Background. An anthropometric whole body model used in different Estonian studies of Kaarma and her co-workers since 1995 has proved to work in assessment of physical peculiarities of the body and its structure regularities in different age groups in both genders. Besides systematization of different body measurements, different authors suggested to use this classification in various applied studies, including medicine. Material and methods. The potential of using body height-weight standard deviation (SD) classification is shown through the example of adolescents (734 students: 352 boys and 382 girls) aged 12-15, who where studied in respect of their sexual maturation (according to suggestions of Tanner) as well as systolic and diastolic blood pressure (BP) (measured with mercury sphygmomanometer on the subject's right arm in a sitting position). Anthropometric variables were measured according to the protocol recommended by the International Society for Advancement of Kinanthropometry (21). All the subjects were assigned into three height / weightconcordant and two height/weight-discordant categories according to the suggestions of Kaarma (11). Results. 1. Differences of the mean maturation signs and mean systolic and diastolic BP values between height-weight categories (HW-categories) were statistically significant for both boys and girls (p < 0.001). 2. In the same age group the mean of the signs studied increased from category I (small) to III (large), and discordant categories (pyknomorphous and leptomorphous) yielded the large category. 3. Sexual development of leptomorphous boys tend to be advanced in comparison with pyknomorphous boys, in girls it was vice versa: pyknomorphous were advanced compared to leptomorphous girls, though this difference was not statistically significant among all the sexual maturation signs. 4. The highest arterial blood pressure values were in the large category of both boys and girls. 5. Boys had elevated blood pressure values more often than girls of the same age group. Results of our study suggested monitoring adolescents of some heightweight categories more carefully, including children of height-weight discordant categories. Conclusion. The use of height-weight SD classification allows finding out whether the differences in the variables studied are related to the body build as a whole or not.
Data on how differences in risk factors, treatments, and outcomes differ between sexes in Europea... more Data on how differences in risk factors, treatments, and outcomes differ between sexes in European countries are scarce. We aimed to study sex-related differences regarding baseline characteristics, in-hospital managements, and mortality of ST-elevation myocardial infarction (STEMI) patients in different European countries. Methods and results
European Heart Journal - Quality of Care and Clinical Outcomes, Mar 1, 2021
To study baseline characteristics, in-hospital managements and mortality of non-ST-elevation myoc... more To study baseline characteristics, in-hospital managements and mortality of non-ST-elevation myocardial infarction (NSTEMI) patients in different European countries.
European Heart Journal - Quality of Care and Clinical Outcomes, Mar 12, 2021
Describe the characteristics, management and outcomes of hospitalized ST-segment elevation myocar... more Describe the characteristics, management and outcomes of hospitalized ST-segment elevation myocardial infarction (STEMI) patients according to national ongoing myocardial infarction registries in Estonia, Hungary, Norway, and Sweden.
Thirty-one scientists met at Aschauhof, Germany to discuss the role of beliefs and self-perceptio... more Thirty-one scientists met at Aschauhof, Germany to discuss the role of beliefs and self-perception on body size. In view of apparent growth stimulatory effects of dominance within the social group that is observed in social mammals, they discussed various aspects of competitive growth strategies and growth adjustments. Presentations included new data from Indonesia, a cohort-based prospective study from Merida, Yucatan, and evidence from recent meta-analyses and patterns of growth in the socially deprived. The effects of stress experienced during pregnancy and adverse childhood events were discussed, as well as obesity in school children, with emphasis on problems when using z-scores in extremely obese children. Aspects were presented on body image in African-American women, and body perception and the disappointments of menopause in view of feelings of attractiveness in different populations. Secular trends in height were presented, including short views on so called 'racial ty...
WNK1-a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) contro... more WNK1-a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control-is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23-4.9), DBP 1.9 mmHg (95%CI:0.7-3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0-1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7610 23 , combined with BRIGHT data-set p = 2610 24 , n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p,10 27). We identified several common haplotypes to be associated with increased BP and multiple low frequency haplotypes significantly associated with lower BP (.10 mmHg reduction) and risk for hypertension (OR,0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH.
The median is denoted as the line that bisects the boxes. The whiskers are lines extending from e... more The median is denoted as the line that bisects the boxes. The whiskers are lines extending from each end of the box covering the extent of the data on 1.5 × interquartile range. Circles represent the outlier values. P-values from Mann-Whitney U-test are shown, applied to test the statistical difference in the distributions of SBP or GFR estimates between two groups.<b>Copyright information:</b>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"http://www.biomedcentral.com/1471-2350/9/25BMC Medical Genetics 2008;9():25-25.Published online 10 Apr 2008PMCID:PMC2330028.
<b>Copyright information:</b>Taken from ", a positional candidate for blood pres... more <b>Copyright information:</b>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"http://www.biomedcentral.com/1471-2350/9/25BMC Medical Genetics 2008;9():25-25.Published online 10 Apr 2008PMCID:PMC2330028.
Singleton polymorphisms were excluded from calculations.<b>Copyright information:</b>... more Singleton polymorphisms were excluded from calculations.<b>Copyright information:</b>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"http://www.biomedcentral.com/1471-2350/9/25BMC Medical Genetics 2008;9():25-25.Published online 10 Apr 2008PMCID:PMC2330028.
Purpose. beach handball is a physically demanding sport. the aim of the study was to establish th... more Purpose. beach handball is a physically demanding sport. the aim of the study was to establish the relationships between anthropometric characteristics and overarm ball speed, a key performance factor. Methods. Overall, 11 male players from the Spanish beach handball national team were recruited. throw speed was assessed in 3 throw types: standing throw (St), standing throw after two steps (rSt), and jump throw with a run-up and self-spin (rSSt). Pearson correlation was used to determine the correlation between variables. Magnitudes were evaluated qualitatively with magnitude-based inference, and the effects of anthropometric variables on the throw tests were analysed with stepwise multiple regression. Results. Maximal throw speed was 25.64 ± 4.14 m • s-1 for St, 23.71 ± 4.24 m • s-1 for rSt, and 24.83 ± 5.49 m • s-1 for rSSt. Large positive correlations were found between throw speed and middle, ring, and little finger lengths (P4 polygon) (r = 0.66 and 0.61 for St and rSSt, respectively). Very large (r = 0.77) and large (r = 0.68) correlations were observed between St and rSt, respectively, and elbow breadth. these results were likely positive for St: P4 (76/24/0), elbow epicondyle distance (EED) (91/9/0); and for rSt: EED (79/21/0); and possibly positive for rSt: P4 (68/32/0). St and rSt were predicted by P4 in 44% and by combining P4 and finger span FS1 in 68%. Conclusions. St and rSt ball speed in beach handball was related to specific hand/elbow anthropometric characteristics which can be easily measured.
The aims of this study were 1. to fix main sexual maturation signs and anthropometric measurement... more The aims of this study were 1. to fix main sexual maturation signs and anthropometric measurements, and 2. to investigate relations between maturational status and main anthropometric parameters (i.e. skinfolds, girths, lengths, breadths/lengths) in 12-15-year old boys. In total, 361 boys from Tartu, Estonia, were studied. Body height and weight, 9 skinfolds, 13 girths, 8 lengths and 8 breadths/lengths were measured. Pubertal stages were determined according to the criteria described by Tanner (1962). Self-assessment of pubic hair (PH1-PH5) was used. Genital development (G1-G5) was estimated by palpating the left testis and matching the size of wood ovoid of the Prader orchidometer. Finally, boys were asked about oigarche (= age at the first ejaculation of sperm). Most of the measured anthropometric variables were significantly different in boys of different chronological age and sexual maturity groups. By linear discriminant analysis, the safety of separation of the chronological age groups was higher than by sexual maturation variables. Nonlinear discriminant analysis allowed to separate sexual maturity groups by anthropometric variables up to 99% security. It was concluded that though the growth and development of a child is highly individual, on an average the anthropometric characteristics alter very constantly with the increase of age and biological maturation. Our results indicated that there were some significant differences in the anthropometrical parameters depending on the chronological age and biological maturation. Mostly length and breadth/length parameters change during the studied age period in respect to sexual development subgroups of boys. The skinfold thicknesses were not changed or even decreased.
The outcome of Genome-Wide Association Studies (GWAS) has challenged the field of blood pressure ... more The outcome of Genome-Wide Association Studies (GWAS) has challenged the field of blood pressure (BP) genetics as previous candidate genes have not been among the top loci in these scans. We used Affymetrix 500K genotyping data of KORA S3 cohort (n = 1,644; Southern-Germany) to address (i) SNP coverage in 160 BP candidate genes; (ii) the evidence for associations with BP traits in genome-wide and replication data, and haplotype analysis. In total, 160 gene regions (genic region610 kb) covered 2,411 SNPs across 11.4 Mb. Marker densities in genes varied from 0 (n = 11) to 0.6 SNPs/kb. On average 52.5% of the HAPMAP SNPs per gene were captured. No evidence for association with BP was obtained for 1,449 tested SNPs. Considerable associations (P,10 23) were detected for the genes, where .50% of HAPMAP SNPs were tagged. In general, genes with higher marker density (.0.2 SNPs/kb) revealed a better chance to reach close to significance associations. Although, none of the detected P-values remained significant after Bonferroni correction (P,0.05/2319, P,2.15610 25), the strength of some detected associations was close to this level: rs10889553 (LEPR) and systolic BP (SBP) (P = 4.5610 25) as well as rs10954174 (LEP) and diastolic BP (DBP) (P = 5.20610 25). In total, 12 markers in 7 genes (ADRA2A, LEP, LEPR, PTGER3, SLC2A1, SLC4A2, SLC8A1) revealed considerable association (P,10 23) either with SBP, DBP, and/or hypertension (HYP). None of these were confirmed in replication samples (KORA S4, HYPEST, BRIGHT). However, supportive evidence for the association of rs10889553 (LEPR) and rs11195419 (ADRA2A) with BP was obtained in meta-analysis across samples stratified either by body mass index, smoking or alcohol consumption. Haplotype analysis highlighted LEPR and PTGER3. In conclusion, the lack of associations in BP candidate genes may be attributed to inadequate marker coverage on the genome-wide arrays, small phenotypic effects of the loci and/or complex interaction with lifestyle and metabolic parameters.
Site/WebVersion.aspx). Determination of genotypes and alleles of rs4343 and rs4291 polymorphisms ... more Site/WebVersion.aspx). Determination of genotypes and alleles of rs4343 and rs4291 polymorphisms of ACE gene was performed at discharge using "iCycler iQ" detection system (BIO-RAD, USA) by TaqMan-assays. Additional exclusion criteria were clinically significant comorbidities. In 36 months after the index event a telephone contact was made with the patients or their relatives to identify the endpoints. We succeeded to specify a patient's status "dead or alive" in 96.6% of cases. In NSTE-ACS and STE-ACS a mortality from any causes was 12.9% (n=22) and 9.9% (n=17) correspondingly, cardiovascular mortality -9.4% (n=16) and 9.4% (n=16) and the incidence of endpoints "cardiovascular death/nonfatal myocardial infarction" -12.8% (n=21) and 15.8% (n=27). Results: A combination of TT genotype of rs4291 polymorphism and GG genotype of rs4343 polymorphism of ACE gene was conclusively associated with three-year total mortality both in STEMI (p=0.02) and in NSTEMI (p<0,0001). However, a statistically significant relationship of these genotypes with cardiovascular mortality as well as the risk of death/nonfatal MI was revealed only in NSTEMI. The ROC-curves analysis showed that in NSTEMI a combined use of GRACE score with rs4291 and rs4343 polymorphisms had significantly (p<0.0001) increased its predictive capability in regard to all previously described endpoints. Thus, the values of the area under ROC-curves in prognosis of total mortality were 0.71 (0.58-0.85) and 0.81 (0.70-0.92) for GRACE and GRACE+ACE scores correspondingly, in prognosis of cardiovascular mortality -0.66 (0.46-0.87) and 0.91 (0.82-0.99) and in prognosis of cardiovascular mortality/nonfatal MI -0.68 (0.55-0.81) and 0.79 (0.68-0.89). As concerns the STE-ACS a significant (p=0.001) improvement of prognostic value of GRACE score supplemented by the identification of rs4291 and rs4343 polymorphisms was obtained only for total mortality within three years. Thus, the values of the area under ROC-curves for GRACE score and the own model (GRACE+ACE) were 0.72 (0.62-0.82) and 0.77 (0.66-0.87 correspondingly. Conclusion: Modification of GRACE 2.0 score by adding the data on the genotypes of rs4291 and rs4343 polymorphisms of ACE gene more effectively improves the mortality prediction within three years after NSTEMI than after STEMI.
On 15 October 2022, 125 years passed from the birth of Juhan Aul (1897-1994), the founder of Esto... more On 15 October 2022, 125 years passed from the birth of Juhan Aul (1897-1994), the founder of Estonian anthropology. The article gives a brief overview of the versatile scientist's contribution to the history of science and anthropology. Some aspects that have been particularly emphasized in his works, presentations and manuscripts and the importance of the anthropological data throughout the ages are highlighted. As a further development of the data collected by Juhan Aul, Markus Valge's doctoral thesis was published in the year of his 125 th birthday.
The aim of the study was to create an anthropometric model that would correlate bodily characteri... more The aim of the study was to create an anthropometric model that would correlate bodily characteristics with nutritional variables. In 131 female students (aged 17–23 years), 32 body measurements and 11 skinfolds were measured and 6 body composition characteristics calculated. In the nutrition study, 24-hour menus were used, where the content of energy and main nutrients – proteins, fats and carbohydrates – was found. The amount of food consumed correlated positively with body density and negatively with weight, circumferences, skinfolds and all indicators of body fat content (r = 0.17 – 0.31). To describe the body as a whole, a 5 SD classification was used with the following body types: (1) small weight, small height; (2) medium weight, medium height; (3) big weight, big height; (4) pycnomorphs (big weight, small height) and (5) leptomorphs (small weight, big height). Food consumption per 1 kg of body weight differed between classes, being relatively high in the class of small subjects and decreasing gradually in the medium and big class. Leptomorphs had significantly higher consumption of energy, fats and carbohydrates compared to pycnics. Consequently, different body measurements can be used to characterize body build, but to characterize the body as a whole, a height-weight classification is needed.
Background: Kidneys have an important function in blood pressure (BP) regulation and elevated BP ... more Background: Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, N-acetyltransferase 8 (NAT8) expressed in embryonic and adult kidney and associated with nephrotoxicity response. Methods/Results: We report the first study exploring NAT8 as a potential candidate gene for blood pressure and kidney function. The resequencing (n = 42, random Estonian samples) identified 15 NAT8 polymorphisms, including 6 novel variants. The diversity of NAT8 5' upstream region (Ï€/ bp = 0.00320) exceeded up to 10 times the variation in the NAT8 genic region (Ï€/bp = 0.00037) as well as the average variation (Ï€/bp = 0.00040) for the promoters of 29 reference genes associated with hypertension. We suggest that a potential source for such high variation could be an active gene conversion process from NAT8B duplicate gene to NAT8. Similarly to NAT8, several reference genes with the most variable upstream regions have also duplicate copies. The NAT8 promoter SNPs were targeted with pilot quantitative association studies for blood pressure (n = 137, healthy unrelated individuals) and for the index of kidney function-estimated glomerular filtration rate (eGFR; n = 157 hypertensives with and without nephropathy). Minor alleles of these polymorphisms revealed a significant protective effect against elevated systolic BP as well as kidney failure in hypertension patients (p < 0.05; linear regression model, addictive effect). Conclusion: The full resequencing and pilot association study of a novel positional candidate gene for blood pressure and renal function, human N-acetyltransferase 8, suggested a contribution of highly variable NAT8 promoter polymorphisms in determination of systolic blood pressure and eGFR. Based on in silico analysis, we raise the hypothesis that the alternative SNP alleles of the NAT8 upstream region may have differential effect on gene expression.
Bivariate body height-weight classification-a useful tool in systematization and analysis of medi... more Bivariate body height-weight classification-a useful tool in systematization and analysis of medical data 27 Bivariate body height-weight classification-a useful tool in systematization and analysis of medical data Background. An anthropometric whole body model used in different Estonian studies of Kaarma and her co-workers since 1995 has proved to work in assessment of physical peculiarities of the body and its structure regularities in different age groups in both genders. Besides systematization of different body measurements, different authors suggested to use this classification in various applied studies, including medicine. Material and methods. The potential of using body height-weight standard deviation (SD) classification is shown through the example of adolescents (734 students: 352 boys and 382 girls) aged 12-15, who where studied in respect of their sexual maturation (according to suggestions of Tanner) as well as systolic and diastolic blood pressure (BP) (measured with mercury sphygmomanometer on the subject's right arm in a sitting position). Anthropometric variables were measured according to the protocol recommended by the International Society for Advancement of Kinanthropometry (21). All the subjects were assigned into three height / weightconcordant and two height/weight-discordant categories according to the suggestions of Kaarma (11). Results. 1. Differences of the mean maturation signs and mean systolic and diastolic BP values between height-weight categories (HW-categories) were statistically significant for both boys and girls (p < 0.001). 2. In the same age group the mean of the signs studied increased from category I (small) to III (large), and discordant categories (pyknomorphous and leptomorphous) yielded the large category. 3. Sexual development of leptomorphous boys tend to be advanced in comparison with pyknomorphous boys, in girls it was vice versa: pyknomorphous were advanced compared to leptomorphous girls, though this difference was not statistically significant among all the sexual maturation signs. 4. The highest arterial blood pressure values were in the large category of both boys and girls. 5. Boys had elevated blood pressure values more often than girls of the same age group. Results of our study suggested monitoring adolescents of some heightweight categories more carefully, including children of height-weight discordant categories. Conclusion. The use of height-weight SD classification allows finding out whether the differences in the variables studied are related to the body build as a whole or not.
Data on how differences in risk factors, treatments, and outcomes differ between sexes in Europea... more Data on how differences in risk factors, treatments, and outcomes differ between sexes in European countries are scarce. We aimed to study sex-related differences regarding baseline characteristics, in-hospital managements, and mortality of ST-elevation myocardial infarction (STEMI) patients in different European countries. Methods and results
European Heart Journal - Quality of Care and Clinical Outcomes, Mar 1, 2021
To study baseline characteristics, in-hospital managements and mortality of non-ST-elevation myoc... more To study baseline characteristics, in-hospital managements and mortality of non-ST-elevation myocardial infarction (NSTEMI) patients in different European countries.
European Heart Journal - Quality of Care and Clinical Outcomes, Mar 12, 2021
Describe the characteristics, management and outcomes of hospitalized ST-segment elevation myocar... more Describe the characteristics, management and outcomes of hospitalized ST-segment elevation myocardial infarction (STEMI) patients according to national ongoing myocardial infarction registries in Estonia, Hungary, Norway, and Sweden.
Thirty-one scientists met at Aschauhof, Germany to discuss the role of beliefs and self-perceptio... more Thirty-one scientists met at Aschauhof, Germany to discuss the role of beliefs and self-perception on body size. In view of apparent growth stimulatory effects of dominance within the social group that is observed in social mammals, they discussed various aspects of competitive growth strategies and growth adjustments. Presentations included new data from Indonesia, a cohort-based prospective study from Merida, Yucatan, and evidence from recent meta-analyses and patterns of growth in the socially deprived. The effects of stress experienced during pregnancy and adverse childhood events were discussed, as well as obesity in school children, with emphasis on problems when using z-scores in extremely obese children. Aspects were presented on body image in African-American women, and body perception and the disappointments of menopause in view of feelings of attractiveness in different populations. Secular trends in height were presented, including short views on so called 'racial ty...
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