Abstract Introduction: AGT gene harbors several variants of which 21 are found to be in high linkage disequilibrium as per Hapmap database. Studies delineating the importance of these tagged SNPs are very limited and lacking from Indian population. In the present study, we evaluated the contribution of four tagged SNPs namely, g.6635G > A, g.6506G > A, g.12840G > A, and g.13828T > C at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to essential hypertension (EHT).
Methods: About 215 hypertensives and 230 normotensives were genotyped for selected tagged SNPs using PCR-RFLP method.
Results: Significant association was obtained for g.6635G > A and g.6506G > A polymorphisms wherein GG homozygotes for both the markers were at risk for developing the condition. g.13828T > C polymorphism specially, female heterozygotes (TC) were found to be at increased risk for EHT. Haplotype GGGC was found to have a significant protective effect (p = 0.0059). Markers g.6506G > A and g.12840G > A resulted in the creation of new enhancer sites thereby affecting splicing process.
Conclusion: The present report is the first one in the literature showing general- and gender-specific association of g.6506G > A and g.13828T > C polymorphisms, respectively, with EHT. However, further studies for replication of present observations are warranted from other populations and other parts of India.
Keywords: Angiotensinogen; essential hypertension; haplotype association; multifactor dimensionality reduction; tagged SNPs.