Association Study With 33 Single-Nucleotide Polymorphisms in 11 Candidate Genes for Hypertension in Chinese

Abstract

Abstract-Essential hypertension is considered to be a typical complex disease with multifactorial etiology, which leads to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of hypertension are not only based on multiple genes with minor effects but also on gene-gene interactions. To test this hypothesis, a case-control study was constructed in Chinese subjects, detecting both single locus and multilocus effects. Eleven candidate genes were selected from biochemical pathways that have been implicated in the development and progression of hypertension, and 33 polymorphisms were evaluated in 503 hypertension patients and 490 age-and gender-matched controls. Single-locus associations, using traditional logistic regression analyses, and multilocus associations, using classification and regression trees and multivariate adaptive regression splines, were both explored in this study. Final models were selected using either Bonferroni correction or cross-validation. Three polymorphisms, TH*rs2070762, ADRB2*Q27E, and GRK4*A486V, were found to be independently associated with essential hypertension in Chinese subjects. In addition to these individual predictors, a potential interaction of CYP11B2-AGTR1 is also involved in the etiology of hypertension. These findings support the multigenic nature of the etiology of essential hypertension and propose a potential gene-gene interactive model for future studies.

Role of GRK4 in the Regulation of Arterial AT1 Receptor in Hypertension

“…In Ghanaians, the two-locus model of angiotensin converting enzyme I/D and GRK4 65L predicts the hypertensive phenotype 70.5% of the time 37 . GRK4 variants, including 65L, 142V, and 486V, by themselves, or interaction with other variants of other genes are associated with hypertension in American Caucasians 39 , Australian Caucasians 12 , Italians 36 and northern Han Chinese 40 . We have reported that hGRK4γ 142V transgenic mice on 98% C57BL/6J background are hypertensive relative to non-transgenic littermates and hGRK4γ WT transgenic mice 6,8,11,13,34 .…”

A46G and C79G polymorphisms in the β2-adrenergic receptor gene (ADRB2) and essential hypertension risk: a meta-analysis

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]27,28 Of the 19 eligible articles, the study of Gu et al 28 was replaced by their earlier report, 10 as these two articles reported the same data. Wu et al 5 provided data on two Chinese minorities, the Hani and Yi, residents of the remote rural area of Yunnan, China.…”

Association of polymorphisms in AGTR1 and AGTR2 genes with primary aldosteronism in the Chinese Han population

“…The underlying rationale of this inconsistency derives from the complexity of the genetic architecture, and must be explained in terms of heredity, variation and evolution. In addition, Gu et al 20 found that a potential interaction of CYP11B2-AGTR1 is involved in the etiology of hypertension. Against the background that the pathogenesis of essential hypertension is undefined, the question of whether secondary hypertension caused by PA follows a similar gene-gene interactive model is worthy of further research.…”