Published Online
on April 24, 2006

A more recent version of this article appeared on June 1, 2006

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Submitted on November 22, 2005
Revised on December 19, 2005

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

Dongfeng Gu^*; Shaoyong Su; Dongliang Ge; Shufeng Chen; Jianfeng Huang; Biao Li; Runsheng Chen; and Boqin Qiang

From the Division of Population Genetics and Prevention (D.Gu, S.S., D.Ge, S.C., J.H.), Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; National Human Genome Center at Beijing (D.Gu, S.S., B.Q.), Beijing, China; Georgia Prevention Institute (D.Ge), Department of Pediatrics, Medical College of Georgia, Augusta; and Institute of Biophysics (B.L., R.C.), Chinese Academy of Sciences, Beijing, China.

^* To whom correspondence should be addressed. E-mail: gudf{at}yahoo.com.

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.

Key words: hypertension, essential • case-control studies • genetics

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