title: Aldehyde dehydrogenase 2 gene is a risk factor for myocardial infarction in Japanese men.
abstract: In epidemiological studies, moderate alcohol consumption has been consistently associated with a reduced risk of myocardial infarction (MI). About half of Japanese show an extremely high sensitivity to alcohol (ethanol), which is due to a missense mutation from glutamic acid (Glu) to lysine (Lys) at codon 487 in an isoenzyme of aldehyde dehydrogenase (ALDH2) with a low Km. We obtained a preliminary result that subjects homozygous for the Lys 487 allele had higher risk for myocardial infarction. The purpose of the present study was to assess this hypothesis by employing a larger cohort of subjects with MI. The experimental group consisted of 342 male subjects with demonstrated MI who were selected randomly from our outpatient clinic. As controls, we employed 1,820 male subjects with no cardiovascular complications who were selected from the Suita Study. All subjects provided their written informed consent to participate in the genetic analyses. Subjects with MI were older and had higher body mass index, higher prevalence of diabetes mellitus, higher prevalence of smoking habit, higher prevalence of the Lys/Lys genotype (homozygous for Lys 487 allele), and lower high density lipoprotein (HDL) cholesterol level (HDL-C). The ALDH2 genotype affected the level of alcohol consumption, and HDL-C. Multiple logistic analyses indicated that the odds ratio of the Lys/Lys genotype to the Lys/Glu+Glu/Glu genotype was 1.56 (p=0.0359). Inclusion of HDL-C as one of the independent variables downplayed the importance of the ALDH2 genotype. This may indicate that the ALDH2 genotype affects MI via its effects on HDL-C. In conclusion, the ALDH2 Lys/Lys genotype is a risk factor for myocardial infarction in Japanese men due to its influence on HDL cholesterol level.
authors.affiliation: Division of Cardiology. National Cardiovascular Center, Suita, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takagi
authors.forename: Naoharu
authors.initials: N
authors.lastname: Iwai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamauchi
authors.forename: Sunao
authors.initials: S
authors.lastname: Kojima
authors.forename: Shinji
authors.initials: S
authors.lastname: Yasuno
authors.forename: Takeshi
authors.initials: T
authors.lastname: Baba
authors.forename: Masahiro
authors.initials: M
authors.lastname: Terashima
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Shoji
authors.initials: S
authors.lastname: Suzuki
authors.forename: Isao
authors.initials: I
authors.lastname: Morii
authors.forename: Sotaro
authors.initials: S
authors.lastname: Hanai
authors.forename: Koh
authors.initials: K
authors.lastname: Ono
authors.forename: Shunroku
authors.initials: S
authors.lastname: Baba
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawamura
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonogi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial