title: Association of Genetically Determined Aldehyde Dehydrogenase 2 Activity with Diabetic Complications in Relation to Alcohol Consumption in Japanese Patients with Type 2 Diabetes Mellitus: The Fukuoka Diabetes Registry.
abstract: Aldehyde dehydrogenase 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. A genetic defect in this enzyme is common in East Asians and determines alcohol consumption behaviors. We investigated the impact of genetically determined ALDH2 activity on diabetic microvascular and macrovascular complications in relation to drinking habits in Japanese patients with type 2 diabetes mellitus. An ALDH2 single-nucleotide polymorphism (rs671) was genotyped in 4,400 patients. Additionally, the relationship of clinical characteristics with ALDH2 activity (ALDH2 *1/*1 active enzyme activity vs. *1/*2 or *2/*2 inactive enzyme activity) and drinking habits (lifetime abstainers vs. former or current drinkers) was investigated cross-sectionally (n = 691 in *1/*1 abstainers, n = 1,315 in abstainers with *2, n = 1,711 in *1/*1 drinkers, n = 683 in drinkers with *2). The multiple logistic regression analysis for diabetic complications was adjusted for age, sex, current smoking habits, leisure-time physical activity, depressive symptoms, diabetes duration, body mass index, hemoglobin A1c, insulin use, high-density lipoprotein cholesterol, systolic blood pressure and renin-angiotensin system inhibitors use. Albuminuria prevalence was significantly lower in the drinkers with *2 than that of other groups (odds ratio [95% confidence interval (CI)]: *1/*1 abstainers as the referent, 0.94 [0.76-1.16] in abstainers with *2, 1.00 [0.80-1.26] in *1/*1 drinkers, 0.71 [0.54-0.93] in drinkers with *2). Retinal photocoagulation prevalence was also lower in drinkers with ALDH2 *2 than that of other groups. In contrast, myocardial infarction was significantly increased in ALDH2 *2 carriers compared with that in ALDH2 *1/*1 abstainers (odds ratio [95% CI]: *1/*1 abstainers as the referent, 2.63 [1.28-6.13] in abstainers with *2, 1.89 [0.89-4.51] in *1/*1 drinkers, 2.35 [1.06-5.79] in drinkers with *2). In summary, patients with type 2 diabetes and ALDH2 *2 displayed a lower microvascular complication prevalence associated with alcohol consumption but a higher macrovascular complication prevalence irrespective of alcohol consumption.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Diabetes Center, Hakujyuji Hospital, Fukuoka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Idewaki
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Diabetes Center, Hakujyuji Hospital, Fukuoka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Iwase
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Division of General Internal Medicine, School of Oral Health Science, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Division of Research Management, Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohkuma
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ide
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shinako
authors.initials: S
authors.lastname: Kaizu
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Jodai
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Udai
authors.initials: U
authors.lastname: Nakamura
authors.affiliation: Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D048909:Diabetes Complications / Q000201:enzymology* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial