Sex-specific differences in the association of a common aldehyde dehydrogenase 2 gene polymorphism and alcohol consumption with stroke risk in a Korean population: a prospective cohort study
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BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehydedehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated withstroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specificassociations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and freeof stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases ofstroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selecteda single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism ofALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baselinequestionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02[1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling foralcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus,and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism wasnot associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism andstroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain morerisk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiablerisk factors of stroke.
Abstract
BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehydedehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated withstroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specificassociations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and freeof stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases ofstroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selecteda single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism ofALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baselinequestionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02[1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling foralcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus,and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism wasnot associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism andstroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain morerisk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiablerisk factors of stroke.
참고문헌 (29)
- Thomasson HR, "Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism", Behav Genet, 23, pp.131~136 (1993)
- Takeuchi F, "Confirmation of ALDH2 as a Major locus of drinking behavior and of its variants regulating multiple metabolic phenotypes in a Japanese population", Circ J, 75, pp.911~918 (2011)
- Baik I, "Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men", Am J Clin Nutr, 93, pp.809~816 (2011)
- Yang SJ, "Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk:a meta-analysis", World J Gastroenterol, 16, pp.4210~4220 (2010)
- Duell EJ, "Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort", Carcinogenesis, 33, pp.361~367 (2012)
- Hiura Y, "A genome-wide association study of hypertension-related phenotypes in a Japanese population", Circ J, 74, pp.2353~2359 (2010)
- Chang YC, "Common ALDH2 genetic variants predict development of hypertension in the SAPPHIRe prospective cohort: gene-environmental interaction with alcohol consumption", BMC Cardiovasc Disord, 12, pp.58~ (2012)
- Suzuki Y, "Association of aldehyde dehydrogenase with inheritance of NIDDM", Diabetologia, 39, pp.1115~1118 (1996)
- Takagi S, "Aldehyde dehydrogenase 2 gene is a risk factor for myocardial infarction in Japanese men", Hypertens Res, 25, pp.677~681 (2002)
- Jo SA, "A Glu487Lys polymorphism in the gene for mitochondrial aldehyde dehydrogenase 2 is associated with myocardial infarction in elderly Korean men", Clin Chim Acta, 382, pp.43~47 (2007)
- Guo YJ, "The ALDH2 Glu504Lys polymorphism is associated with coronary artery disease in Han Chinese: Relation with endothelial ADMA levels", Atherosclerosis, 211, pp.545~550 (2010)
- Chen CH, "Mitochondrial aldehyde dehydrogenase and cardiac diseases", Cardiovasc Res, 88, pp.51~57 (2010)
- Yao CT, "The role of ALDH2 and ADH1B polymorphism in alcohol consumption and stroke in Han Chinese", Hum Genomics, 5, pp.569~576 (2011)
- Reynolds K, "Alcohol consumption and risk of stroke: a meta-analysis", JAMA, 289, pp.579~588 (2003)
- Lee JY, "A genome-wide association study of a coronary artery disease risk variant", J Hum Genet, 58, pp.120~126 (2013)
- Cho YS, "A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits", Nat Genet, 41, pp.527~534 (2009)
- Bierut LJ, "ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry", Mol Psychiatry, 17, pp.445~450 (2012)
- Li H, "Refined geographic distribution of the oriental ALDH2 * 504Lys (nee 487Lys)variant", Ann Hum Genet, 73, pp.335~345 (2009)
- Takeshita T, "Self-reported alcohol-associated symptoms and drinking behavior in three ALDH2 genotypes among Japanese university students", Alcohol Clin Exp Res, 23, pp.1065~1069 (1999)
- Nagasawa H, "A polymorphism of the aldehyde dehydrogenase 2 gene is a risk factor for multiple lacunar infarcts in Japanese men: the Takahata Study", Eur J Neurol, 14, pp.428~434 (2007)
- Zee RY, "Prospective evaluation of the alcohol dehydrogenase gamma1", gamma2 gene polymorphism and risk of stroke, 2004, pp.35, e39~e42
- Drogan D, "Alcohol consumption, genetic variants in alcohol deydrogenases, and risk of cardiovascular diseases: a prospective study and meta-analysis", PLoS One, 7, pp.e32176~ (2012)
- Riemann R, "The influence of nocturnal alcohol ingestion on snoring", Eur Arch Otorhinolaryngol, 267, pp.1147~1156 (2010)
- Koskenvuo M, "Snoring as a risk factor for ischaemic heart disease and stroke in men", Br Med J (Clin Res Ed), 294, pp.16~19 (1987)
- Hu FB, "Snoring and risk of cardiovascular disease in women", J Am Coll Cardiol, 35, pp.308~313 (2000)
- Sands M, "Self-reported snoring and risk of cardiovascular disease among postmenopausal women (from the Women's Health Initiative)", Am J Cardiol, 111, pp.540~546 (2013)
- Chen CH, "Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart", Science, 321, pp.1493~1495 (2008)
- Mackenzie IS, "Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans", Arterioscler Thromb Vasc Biol, 25, pp.1891~1895 (2005)
- Gorelick PB, "Alcohol and stroke", Stroke, 18, pp.268~271 (1987)