Common single nucleotide polymorphisms in Japanese patients with essential hypertension: aldehyde dehydrogenase 2 gene as a risk factor independent of alcohol consumption.
Essential hypertension (EH) is a multifactorial disorder determined by the interaction of environmental and genetic factors. EH patients' responses to these factors may vary, depending on differences in their genes that determine the physiological systems that mediate the response. The purpose of this investigation was to clarify the contributions of genetic background and lifestyle to EH through an association study using some common single nucleotide polymorphisms (SNPs) that should have functional effects on EH phenotypes. We studied the associations between common SNPs of some causal genes related to EH and lifestyle in a Japanese population. The variants of the causal genes were selected based on their functions, including: obesity (adrenergic, beta-3-, receptor: ADRB3), alcohol consumption (aldehyde dehydrogenase 2: ALDH2), water-electrolyte metabolism (guanine nucleotide binding protein [G protein], beta polypeptide 3: GNB3), glycometabolism (peroxisome proliferator-activated receptor gamma: PPARG), lipometabolism (cholesteryl ester transfer protein, plasma: CETP), atherosclerosis (5,10-methylenetetrahydrofolate reductase [NADPH]: MTHFR), and cellular behavior (gap junction protein, alpha 4, 37 kD: GJA4). Case-control association analysis showed a significant association between EH and both the ALDH2 (Lys487Glu) and GNB3 (C825T) variants. Logistic regression analysis indicated that body mass index (BMI) is an important risk factor for EH, and that the GG (Glu/Glu) genotype of ALDH2 was an independent risk factor for EH overall and especially for EH in males. There was no interaction between the ALDH2 genotype and alcohol consumption overall or in male subjects. Our results suggest that the ALDH2 genotype is associated with EH independently of alcohol consumption.
Hui
Peng
P
Division of Molecular Diagnostics, Advanced Medical Research Center, Nihon University School of Medicine, Ooyaguchi-kamimachi, Tokyo, Japan.
Nakayama
Tomohiro
T
Morita
Akihiko
A
Sato
Naoyuki
N
Hishiki
Mikano
M
Saito
Kosuke
K
Yoshikawa
Yukie
Y
Tamura
Masaaki
M
Sato
Ichiro
I
Takahashi
Teruyuki
T
Soma
Masayoshi
M
Izumi
Yoichi
Y
Ozawa
Yukio
Y
Cheng
Zuheng
Z
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D007564:Japan; D008019:Life Style; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics