title: 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.
abstract: OBJECTIVE
  It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population.
  
  
  METHODS
  We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire.
  
  
  RESULTS
  Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism 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 for alcohol 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 was not associated with stroke risk.
  
  
  CONCLUSIONS
  The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.
authors: Department of Internal Medicine, Korea University Ansan Hospital, Ansan 425-707, Korea. ; Institute of Human Genomic Study, Korea University Ansan Hospital, Ansan 425-707, Korea.
authors: Chol
authors: C
authors: Shin
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam 463-712, Korea.
authors: KyuBum
authors: K
authors: Kwack
authors: Department of Preventive Medicine, Ajou University School of Medicine, Suwon 443-380, Korea.
authors: Nam H
authors: NH
authors: Cho
authors: Department of Internal Medicine, Korea University Ansan Hospital, Ansan 425-707, Korea.
authors: Seong Hwan
authors: SH
authors: Kim
authors: Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, 77 Jeongneung-ro Seongbuk-gu Seoul 136-702, Korea.
authors: Inkyung
authors: I
authors: Baik
keywords: ALDH2 polymorphism; alcohol consumption; prospective study; stroke