Association study with 33 single-nucleotide polymorphisms in 11 candidate genes for hypertension in Chinese.
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.
Gu
Dongfeng
D
Division of Population Genetics and Prevention, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. gudf@yahoo.com
Su
Shaoyong
S
Ge
Dongliang
D
Chen
Shufeng
S
Huang
Jianfeng
J
Li
Biao
B
Chen
Runsheng
R
Qiang
Boqin
B
D000409:Alanine; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D054771:G-Protein-Coupled Receptor Kinase 4; D018698:Glutamic Acid; D005973:Glutamine; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D014633:Valine
D044140:Receptor, Angiotensin, Type 1; D018343:Receptors, Adrenergic, beta-2; D005973:Glutamine; D018698:Glutamic Acid; D019405:Cytochrome P-450 CYP11B2; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human; D014633:Valine; D000409:Alanine