Impact of genetic variations and biochemical parameters on blood pressure: A study in families with a hypertensive proband.

摘要

Although essential hypertension has long been recognized to involve a strong genetic predisposition, the genes that increase susceptibility remain virtually unknown. With recent advances in molecular biology and statistical methods, it has become feasible to study candidate genes which may contribute to the pathogenesis of essential hypertension in humans. We identified the polymorphisms of five genes by applying a micoarray genotyping system for multiplex analysis of a panel of single nucleotide polymorphisms (SNPs) in genes involved in the regulation of blood pressure, then determined whether specific SNPs in genes were related to blood pressure in Hong Kong Chinese.; Twelve SNPs in five candidate genes, which included the M235T, T174M, G-217A and L10F polymorphisms of the angiotensinogen gene (AGT); A-48G polymorphism of the dopamine D1 receptor gene (DD1R); the TaqI A, -141C Ins/Del and A-241G polymorphisms of the dopamine D2 receptor gene (DD2R); Phe382Val, Lys460Glu, and Gly1008Val polymorphisms of the insulin receptor gene (INSR); and the A-3826G polymorphism of the uncoupling protein 1 gene (UCP1).; Families were recruited if the proband was found to have hypertension and had siblings resident in Hong Kong. We identified 126 families with at least one hypertensive sibling. A total of 434 siblings were studied. All subjects underwent clinical and biochemical investigation to exclude those with either secondary hypertension, impaired glucose tolerance or type 2 diabetes mellitus.; Based on the study results, we conclude that blood pressure levels are determined by complex interactions between genetic and environmental factors. The AGT gene 235T and the DD1R gene -48G alleles strongly predicted the development of hypertension in Hong Kong Chinese. The variants of the DD2R gene and the UCP1 gene A-3826G variant only weakly impacted upon blood regulation. However, the three variants of the INSR gene and the L10F variant of the AGT gene were not detected in Hong Kong Chinese. Although success in identifying single genes contributing to hypertension has been limited, the use of intermediate phenotypes and dense mapping of candidate genes shows the influence of gene-gene interaction on hypertension or obesity-related hypertension in our hypertensive families of Hong Kong Chinese.