Estimation of risk and interaction of single nucleotide polymorphisms at angiotensinogen locus causing susceptibility to essential hypertension: a case control study

Abstract

Introduction:The risk conferred by the variants and haplotypes of single nucleotide polymorphisms (SNPs) at human angiotensinogen (AGT) gene to essential hypertension (EHT) have been described in several populations with variations in the results attributed to their ethnicity. We attempted to evaluate the risk of -217G>A, -152G>A, -20A>C, -6G>A, T174M, M235T and 15241A>G polymorphisms at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to EHT. Method: Two-hundred and forty-nine hypertensives and 248 controls were genotyped for the selected markers. Results: Study of demographic parameters revealed significant association of obesity, positive family history and nonvegetarian diet habit, suggesting elevated risk of the condition when associated with these parameters. Significantly high risk for males with AA genotype of -217G>A polymorphism was observed for developing EHT (p = .07). Males with -217A (p = .01) showed a two-fold higher risk for EHT. Markers -217G>A and -6G>A were in strong linkage disequilibrium in patients as compared to controls. Strong epistatic interactions were found between -6G>A, M235T and -217G>A markers, supporting the synergistic effect between them leading to EHT. Conclusion: Our findings suggest that -217A variant is significantly associated with the risk for EHT in males. Further studies on the functional role of the marker -217 are recommended for understanding the cause of association with EHT. KeywordsEssential hypertension (EHT), angiotensinogen (AGT), linkage disequilibrium (LD), multifactor dimensionality reduction (MDR), single nucleotide polymorphism (SNP), haplotype association, epistatic interaction, statistical package for social sciences (SPSS)

Gender Specific Association of RAS Gene Polymorphism with Essential Hypertension: A Case-Control Study

“…However, previous studies in south India mainly focus on limited gene of RAS [47, 48, 51]; thus we carried out a case-control study to systemically investigate the association between polymorphisms in RAS genes and essential hypertension. The present study identifies gender specific genetic variants in RAS genes that may play crucial roles in BP regulation and susceptibility for hypertension.…”

Impact of interactions between risk alleles on clinical endpoints in hypertension

“…Of note, the attributed inconsistencies and the magnitude of low power to detect an association with individual SNPs can be improved using gene–gene interaction analysis 36 37. The epistatic evaluation in multifactorial disease like EH further increases the predictive accuracy of genotype–phenotype correlations 7.…”

Polymorphisms of +2836 G>A in the apoE gene are strongly associated with the susceptibility to essential hypertension in the Chinese Hui population

“…Furthermore, recent molecular epidemiology studies revealed that certain genetic variants are associated with susceptibility to hypertension. In particular, polymorphisms of genes, including the leptin receptor, angiotensinogen, cytochrome P450, vascular endothelial growth factor, adrenoceptor, ApoB, bradykinin beta 2 receptor, and apolipoprotein CIII, have been associated with the susceptibility to this disease (Charita et al, 2012;Fowdar et al, 2012;Gu et al, 2012;Hamedian et al, 2012;Li and Liu, 2012;Shin et al, 2012;Tang et al, 2012;Xi et al, 2012b). Similar to variants of other genes in the apolipoprotein family, apoE gene polymorphisms may also contribute to the occurrence of hypertension in various populations.…”