Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2012

Open Access 01-12-2012 | Research article

Common ALDH2 genetic variants predict development of hypertension in the SAPPHIRe prospective cohort: Gene-environmental interaction with alcohol consumption

Authors: Yi-Cheng Chang, Yen-Feng Chiu, I-Te Lee, Low-Tone Ho, Yi-Jen Hung, Chao A Hsiung, Thomas Quertermous, Timothy Donlon, Wei-Jei Lee, Po-Chu Lee, Che-Hong Chen, Daria Mochly-Rosen, Lee-Ming Chuang

Published in: BMC Cardiovascular Disorders | Issue 1/2012

Login to get access

Abstract

Background

Genetic variants near/within the ALDH2 gene encoding the mitochondrial aldehyde dehydrogenase 2 have been associated with blood pressure and hypertension in several case–control association studies in East Asian populations.

Methods

Three common tag single nucleotide polymorphisms (tagSNP) in the ALDH2 gene were genotyped in 1,134 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family cohort. We examined whether the ALDH2 SNP genotypes predicted the development of hypertension in the prospective SAPPHIRe cohort.

Results

Over an average follow-up period of 5.7 years, carriers homozygous for the rs2238152 T allele in the ALDH2 gene were more likely to progress to hypertension than were non-carriers (hazard ratio [HR], 2.88, 95% confidence interval [CI], 1.06-7.84, P = 0.03), corresponding to a population attributable risk of ~7.1%. The risk associated with the rs2238152 T allele were strongest in heavy/moderate alcohol drinkers and was reduced in non-drinkers, indicating an interaction between ALDH2 genetic variants and alcohol intake on the risk of hypertension (P for interaction = 0.04). The risk allele was associated with significantly lower ALDH2 gene expression levels in human adipose tissue.

Conclusion

ALDH2 genetic variants were associated with progression to hypertension in a prospective Chinese cohort. The association was modified by alcohol consumption.
Appendix
Available only for authorised users
Literature
1.
go back to reference Hurley TD, Edenberg HJ, Li TK: Pharmacogenomics of alcoholism in Pharmacogenomics: The Search for Individualized Therapies. . 2002, : 417-441. Hurley TD, Edenberg HJ, Li TK: Pharmacogenomics of alcoholism in Pharmacogenomics: The Search for Individualized Therapies. . 2002, : 417-441.
2.
go back to reference Enomoto N, Takase S, Yasuhara M, et al: Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcohol Clin Exp Res. 1991, 15: 141-144. 10.1111/j.1530-0277.1991.tb00532.x.CrossRefPubMed Enomoto N, Takase S, Yasuhara M, et al: Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcohol Clin Exp Res. 1991, 15: 141-144. 10.1111/j.1530-0277.1991.tb00532.x.CrossRefPubMed
3.
go back to reference Perez-Miller S, Younus H, Vanam R, et al: Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant. Nat Struct Mol Biol. 2010, 17: 159-164. 10.1038/nsmb.1737.CrossRefPubMedPubMedCentral Perez-Miller S, Younus H, Vanam R, et al: Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant. Nat Struct Mol Biol. 2010, 17: 159-164. 10.1038/nsmb.1737.CrossRefPubMedPubMedCentral
4.
go back to reference Peng GS, Chen YC, Tsao TP, et al: Pharmacokinetic and pharmacodynamic basis for partial protection against alcoholism in Asians, heterozygous for the variant ALDH2*2 gene allele. Pharmacogenet Genomics. 2007, 17: 845-855. 10.1097/FPC.0b013e3282609e67.CrossRefPubMed Peng GS, Chen YC, Tsao TP, et al: Pharmacokinetic and pharmacodynamic basis for partial protection against alcoholism in Asians, heterozygous for the variant ALDH2*2 gene allele. Pharmacogenet Genomics. 2007, 17: 845-855. 10.1097/FPC.0b013e3282609e67.CrossRefPubMed
5.
go back to reference Tottmar O, Hellstrom E: Blood pressure response to ethanol in relation to acetaldehyde levels and dopamine-beta-hydroxylase activity in rats pretreated with disulfiram, cyanamide and coprine. Acta Pharmacol Toxicol (Copenh). 1979, 45: 272-281.CrossRef Tottmar O, Hellstrom E: Blood pressure response to ethanol in relation to acetaldehyde levels and dopamine-beta-hydroxylase activity in rats pretreated with disulfiram, cyanamide and coprine. Acta Pharmacol Toxicol (Copenh). 1979, 45: 272-281.CrossRef
6.
go back to reference Brown RA, Savage AO: Effects of acute acetaldehyde, chronic ethanol, and argyline treatment on agonist responses of the rat aorta. Toxicol Appl Pharmacol. 1996, 136: 170-178. 10.1006/taap.1996.0021.CrossRefPubMed Brown RA, Savage AO: Effects of acute acetaldehyde, chronic ethanol, and argyline treatment on agonist responses of the rat aorta. Toxicol Appl Pharmacol. 1996, 136: 170-178. 10.1006/taap.1996.0021.CrossRefPubMed
7.
go back to reference Satoh Y, Ide Y, Sugano T, et al: Hypotensive and hypertensive effects of acetaldehyde on blood pressure in rats. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2008, 43: 188-193.PubMed Satoh Y, Ide Y, Sugano T, et al: Hypotensive and hypertensive effects of acetaldehyde on blood pressure in rats. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2008, 43: 188-193.PubMed
8.
go back to reference Chen Z, Stamler JS: Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase. Trends Cardiovasc Med. 2006, 16: 259-265. 10.1016/j.tcm.2006.05.001.CrossRefPubMed Chen Z, Stamler JS: Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase. Trends Cardiovasc Med. 2006, 16: 259-265. 10.1016/j.tcm.2006.05.001.CrossRefPubMed
9.
go back to reference Mackenzie IS, Maki-Petaja KM, McEniery CM, et al: Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans. Arterioscler Thromb Vasc Biol. 2005, 25: 1891-1895. 10.1161/01.ATV.0000179599.71086.89.CrossRefPubMed Mackenzie IS, Maki-Petaja KM, McEniery CM, et al: Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans. Arterioscler Thromb Vasc Biol. 2005, 25: 1891-1895. 10.1161/01.ATV.0000179599.71086.89.CrossRefPubMed
10.
go back to reference Amamoto K, Okamura T, Tamaki S, et al: Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population. Hypertens Res. 2002, 25: 857-864. 10.1291/hypres.25.857.CrossRefPubMed Amamoto K, Okamura T, Tamaki S, et al: Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population. Hypertens Res. 2002, 25: 857-864. 10.1291/hypres.25.857.CrossRefPubMed
11.
go back to reference Takagi S, Baba S, Iwai N, et al: The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: the Suita study. Hypertens Res. 2001, 24: 365-370. 10.1291/hypres.24.365.CrossRefPubMed Takagi S, Baba S, Iwai N, et al: The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: the Suita study. Hypertens Res. 2001, 24: 365-370. 10.1291/hypres.24.365.CrossRefPubMed
12.
go back to reference Hashimoto Y, Nakayama T, Futamura A, et al: Relationship between genetic polymorphisms of alcohol-metabolizing enzymes and changes in risk factors for coronary heart disease associated with alcohol consumption. Clin Chem. 2002, 48: 1043-1048.PubMed Hashimoto Y, Nakayama T, Futamura A, et al: Relationship between genetic polymorphisms of alcohol-metabolizing enzymes and changes in risk factors for coronary heart disease associated with alcohol consumption. Clin Chem. 2002, 48: 1043-1048.PubMed
13.
go back to reference Hui P, Nakayama T, Morita A, et al: Common single nucleotide polymorphisms in Japanese patients with essential hypertension: aldehyde dehydrogenase 2 gene as a risk factor independent of alcohol consumption. Hypertens Res. 2007, 30: 585-592. 10.1291/hypres.30.585.CrossRefPubMed Hui P, Nakayama T, Morita A, et al: Common single nucleotide polymorphisms in Japanese patients with essential hypertension: aldehyde dehydrogenase 2 gene as a risk factor independent of alcohol consumption. Hypertens Res. 2007, 30: 585-592. 10.1291/hypres.30.585.CrossRefPubMed
14.
go back to reference Saito K, Yokoyama T, Yoshiike N, et al: Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure?. Hypertens. 2003, 21: 1097-1105. 10.1097/00004872-200306000-00009.CrossRef Saito K, Yokoyama T, Yoshiike N, et al: Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure?. Hypertens. 2003, 21: 1097-1105. 10.1097/00004872-200306000-00009.CrossRef
15.
go back to reference Tsuritani I, Ikai E, Date T, et al: Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship. Am J Hypertens. 1995, 8: 1053-1059. 10.1016/0895-7061(95)00222-B.CrossRefPubMed Tsuritani I, Ikai E, Date T, et al: Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship. Am J Hypertens. 1995, 8: 1053-1059. 10.1016/0895-7061(95)00222-B.CrossRefPubMed
16.
go back to reference Hiura Y, Tabara Y, Kokubo Y, et al: A genome-wide association study of hypertension-related phenotypes in a Japanese population. Circ J. 2001, 74: 2353-2359.CrossRef Hiura Y, Tabara Y, Kokubo Y, et al: A genome-wide association study of hypertension-related phenotypes in a Japanese population. Circ J. 2001, 74: 2353-2359.CrossRef
17.
go back to reference Chen L, Davey Smith G, Harbord RM: Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach. PLoS Med. 2008, 5: e52-10.1371/journal.pmed.0050052.CrossRefPubMedPubMedCentral Chen L, Davey Smith G, Harbord RM: Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach. PLoS Med. 2008, 5: e52-10.1371/journal.pmed.0050052.CrossRefPubMedPubMedCentral
18.
go back to reference Kato N, Takeuchi F, Tabara Y, et al: Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet. 2011, 43: 531-538. 10.1038/ng.834.CrossRefPubMedPubMedCentral Kato N, Takeuchi F, Tabara Y, et al: Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet. 2011, 43: 531-538. 10.1038/ng.834.CrossRefPubMedPubMedCentral
19.
20.
go back to reference Ranade K, Wu KD, Risch N, et al: Genetic variation in aldosterone synthase predicts plasma glucose levels. Proc Natl Acad Sci USA. 2001, 98: 13219-13224. 10.1073/pnas.221467098.CrossRefPubMedPubMedCentral Ranade K, Wu KD, Risch N, et al: Genetic variation in aldosterone synthase predicts plasma glucose levels. Proc Natl Acad Sci USA. 2001, 98: 13219-13224. 10.1073/pnas.221467098.CrossRefPubMedPubMedCentral
21.
go back to reference Hwu CM, Hsiao CF, Kuo SW, et al: Physical inactivity is an important lifestyle determinant of insulin resistance in hypertensive patients. Blood Press. 2004, 13: 355-361. 10.1080/08037050410004828.CrossRefPubMed Hwu CM, Hsiao CF, Kuo SW, et al: Physical inactivity is an important lifestyle determinant of insulin resistance in hypertensive patients. Blood Press. 2004, 13: 355-361. 10.1080/08037050410004828.CrossRefPubMed
22.
go back to reference Consortium HM: A haplotype map of the human genome. Nature. 2005, 437: 1299-1320. 10.1038/nature04226.CrossRef Consortium HM: A haplotype map of the human genome. Nature. 2005, 437: 1299-1320. 10.1038/nature04226.CrossRef
23.
go back to reference Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21: 263-265. 10.1093/bioinformatics/bth457.CrossRefPubMed Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21: 263-265. 10.1093/bioinformatics/bth457.CrossRefPubMed
24.
go back to reference Abecasis GR, Cardon LR, Cookson WO: A general test of association for quantitative traits in nuclear families. Am J Hum Genet. 2000, 66: 279-292. 10.1086/302698.CrossRefPubMed Abecasis GR, Cardon LR, Cookson WO: A general test of association for quantitative traits in nuclear families. Am J Hum Genet. 2000, 66: 279-292. 10.1086/302698.CrossRefPubMed
25.
go back to reference Nyholt DR: A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet. 2004, 74: 765-769. 10.1086/383251.CrossRefPubMedPubMedCentral Nyholt DR: A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet. 2004, 74: 765-769. 10.1086/383251.CrossRefPubMedPubMedCentral
26.
go back to reference Wu Y, Huxley R, Li L, et al: Prevalence, awareness, treatment, and control of hypertension in China: data from the China National Nutrition and Health Survey 2002. Circulation. 2008, 118: 2679-2686. 10.1161/CIRCULATIONAHA.108.788166.CrossRefPubMed Wu Y, Huxley R, Li L, et al: Prevalence, awareness, treatment, and control of hypertension in China: data from the China National Nutrition and Health Survey 2002. Circulation. 2008, 118: 2679-2686. 10.1161/CIRCULATIONAHA.108.788166.CrossRefPubMed
Metadata
Title
Common ALDH2 genetic variants predict development of hypertension in the SAPPHIRe prospective cohort: Gene-environmental interaction with alcohol consumption
Authors
Yi-Cheng Chang
Yen-Feng Chiu
I-Te Lee
Low-Tone Ho
Yi-Jen Hung
Chao A Hsiung
Thomas Quertermous
Timothy Donlon
Wei-Jei Lee
Po-Chu Lee
Che-Hong Chen
Daria Mochly-Rosen
Lee-Ming Chuang
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2012
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/1471-2261-12-58

Other articles of this Issue 1/2012

BMC Cardiovascular Disorders 1/2012 Go to the issue