High risk for essential hypertension in males conferred by g.15241A>G polymorphism in intron 3 of AGT gene.

A total of 180 hypertensive and 188 normotensive subjects were studied for demographic features and for variations in exon 4 including exon-intron boundary of AGT gene using single-strand conformation polymorphism analysis. Sequencing of the samples showing mobility shift revealed a single-nucleotide polymorphism variant g.15241A>G in intron 3 of the gene. The polymorphism was consistent with Hardy-Weinberg equilibrium in both the cases and the controls. Although the genotype distribution and allele frequencies did not differ significantly in general, high risk was observed for males with G allele (OR = 2.08; 95% CI = 1.02-4.21; P = .04). Similar results were obtained when the genotypes were tested in dominant model wherein G allele carriers were found to be at twofold risk for developing essential hypertension (OR = 2.09; 95% CI = 0.99-4.41; P = 0.05). This report is the first one in the literature showing association of g.15241A>G polymorphism with a clinical condition.

Association and interaction of -58C>T and ±9 bp polymorphisms of BDKRB2 gene causing susceptibility to essential hypertension.

INTRODUCTION: Bradykinin, a vasodilator by nature has been documented to have a protective role against hypertension and cardiovascular complications. Polymorphisms of bradykinin B2 receptor (BDKRB2) gene are reported to be predisposing factors for hypertension. Evaluation of the association between -58C>T and ±9 bp polymorphisms of BDKRB2 with essential hypertension (EHT) was attempted. METHODS: Two hundred and fourteen primary hypertensives and 249 controls were genotyped for the selected markers by polymerase chain reaction, gel electrophoresis (±9 bp), and SSCP (-58C>T). RESULTS: While -58C>T polymorphism did not reveal any association with EHT, ±9 bp polymorphism showed a significant association with high risk for heterozygotes (+9/-9) when tested against the pooled frequencies of homozygotes (OR [odds ratio] = 1.63, 95% confidence interval [CI] = 1.12-2.38, P = .02), and this risk was 1.7 folds high in males (OR = 1.74, 95% CI = 1.05-2.86, P = .06) and 1.9 folds high in familial cases (OR = 1.96, 95% CI = 1.09-3.53, P = .04). In contrast, significant protective effect was observed for -9/-9 genotype against EHT when tested under dominant model in general (OR = 0.59, 95% CI = 0.41-0.86, P = .01), in males (OR = 0.49, 95% CI = 0.30-0.82, P = .01), and in familial cases (OR = 0.50, 95% CI = 0.28-0.89, P = .04). Significant risk for +9 bp allele was observed in general (OR = 1.39, 95% CI = 1.05-1.86, P = .04) and in males (OR = 1.65, 95% CI = 1.13-2.41, P = .02). The interaction information analysis revealed a synergistic effect between the two polymorphisms contributing to EHT. +9/+9 genotype of ±9 bp polymorphism when present in combination with CC genotype of -58C>T polymorphism showed 2.2-fold higher risk for developing EHT. CONCLUSIONS: The results suggest that allele +9 bp might be a risk factor for EHT in general and specially in males. Markers -58C>T and ±9 bp may act synergistically causing susceptibility to EHT.

Association of shorter telomere length with essential hypertension in Indian population.

OBJECTIVES: Essential hypertension is known to be associated with growth, development, and aging of humans. Telomeres are specialized nucleoprotein complexes consisting of tandem repeats of DNA sequences (TTAGGG)n that serve as protective caps of human chromosomes. Telomere length is considered as a biomarker of aging in somatic cells. In the present investigation, leukocyte telomere length was determined among hypertensive and normal individuals to find out the association, if any, with hypertension. MATERIALS AND METHODS: Venous blood samples were collected from normal and hypertensive individuals with written informed consent approved by ethic committee of Department of Genetics, Osmania University Hyderabad, India. Genomic DNA was isolated from blood samples of 98 normal (age range: 30-70 years, mean age: 51.01 ± 10.12 years) and 96 hypertensive individuals (age range: 35-75 years, mean age: 49.18 ± 6.46 years). Using a SYBR green-based real time quantitative PCR relative telomere length was determined among these individuals. RESULTS: The relative telomere length (T/S ratio) in hypertensive individuals was observed to be 0.91 ± 0.16 which was significantly different (P < 0.001) from normal individuals where the relative telomere length was 0.99 ± 0.13. No significant difference was observed between relative telomere length of male and female individuals, although there is negative correlation between age and telomere length was observed in both normal and hypertensive individuals. The systolic and diastolic blood pressure was negatively correlated with relative telomere length, though not significant. CONCLUSION: Shorter telomere length is associated with hypertensive individuals in Indian population.