Linkage of angiotensinogen gene polymorphisms with hypertension in a sibling study of Hong Kong Chinese

Abstract

The angiotensinogen gene has been linked with human essential hypertension in whites but the relationship in Asian populations has been less consistent. This study aimed to examine genetic associations between hypertension and the M235T, T174M, and G-217A polymorphisms of the angiotensinogen gene in Chinese siblings. We studied members of 126 families with a hypertensive proband, including 434 siblings, of which 178 were hypertensive. Parental history of hypertension was recorded. The M235T, T174M, and G-217A polymorphisms were examined using a microarray method, validated by sequencing. The transmission disequilibrium test was applied to identify whether the genetic polymorphism loci were related to hypertension. Haplotype analysis of the combined polymorphisms was applied using the TRANSMIT program. Linkage study was conducted by applying the affected pedigree member method. A significant overtransmission was observed for the T235 allele at the M235T polymorphism and hypertension (chi2 = 4.41, P = 0.036) but not for the T174M and G-217A polymorphisms. The haplotype analysis showed a significant association with the haplotypes of paired markers (T174 and T235) with chi2 value of 8.131 (P = 0.004; global test chi2 = 9.131, P = 0.028). Linkage between M235T and hypertension was detected (T = -2.25, P = 0.019), and a tendency for linkage with central obesity-related hypertension was found for the M235T and T174M polymorphisms (P = 0.0087 and P = 0.01). The M235T and T174M variants, especially the T235 allele, contribute to an increased risk of hypertension in these Chinese patients.