11deea42-5057-47d5-b026-eb8baa9ddd54
title
Three single-nucleotide polymorphisms of the  angiotensinogen  gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis.
08795029-000e-4a1b-9f68-c5bc19af0e1c
abstract
Although some single polymorphism analyses of the  angiotensinogen  ( AGT ) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single-nucleotide polymorphisms (SNPs) ( G-217A ,  A-6G , and  M235T ) in the  AGT  gene with hypertension. In a sample of 461 hypertensive and 327 normotensive patients in Taiwan, we found that  -217AA  and  -6GG  homozygotes conferred independently an increased risk to hypertension (P = 0.008 and P = 0.037, respectively), as illustrated by their significant associations with hypertension in both single SNP and pair-wise SNPs analyses. Meanwhile, a very weak linkage disequilibrium was found between the  G-217A  and the  A-6G  polymorphisms in terms of r2 (<0.05). On the basis of likelihood ratio test, only the set of haplotypes that constituted the  A-6G  and the  M235T  polymorphisms was associated with hypertension (chi2 = 20.91, P = 0.0008), which was mainly due to the increased frequency of the recombinant haplotypes ( -6A  identical with 235M and  -6G  identical with 235T), and a pathophysiological role in the predisposition to hypertension was hence indicated. In functional assays, the promoter activities of the haplotypes  -217A  identical with  -6A  and  -217G  identical with  -6G  were significantly higher than the most common haplotype  -217G  identical with  -6A . These results highlight the necessity of a thorough analysis of all reported variants of a candidate gene in the elucidation of genetic susceptibility to a complex disease like hypertension, even when the variants are in the same haplotype block.