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 singlenucleotide 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.
| Original language | English |
|---|---|
| Article number | e0143288 |
| Journal | PloS one |
| Volume | 10 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2015 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- General
Cite this
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. / Idewaki, Yasuhiro; Iwase, Masanori; Fujii, Hiroki; Ohkuma, Toshiaki; Ide, Hitoshi; Kaizu, Shinako; Jodai, Tamaki; Kikuchi, Yohei; Hirano, Atsushi; Nakamura, Udai; Kubo, Michiaki; Kitazono, Takanari.
In: PloS one, Vol. 10, No. 11, e0143288, 01.11.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association of genetically determined aldehyde dehydrogenase 2 activity with diabetic complications in relation to alcohol consumption in Japanese patients with type 2 diabetes mellitus
T2 - The fukuoka diabetes registry
AU - Idewaki, Yasuhiro
AU - Iwase, Masanori
AU - Fujii, Hiroki
AU - Ohkuma, Toshiaki
AU - Ide, Hitoshi
AU - Kaizu, Shinako
AU - Jodai, Tamaki
AU - Kikuchi, Yohei
AU - Hirano, Atsushi
AU - Nakamura, Udai
AU - Kubo, Michiaki
AU - Kitazono, Takanari
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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 singlenucleotide 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.
AB - 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 singlenucleotide 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84957869054&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0143288
DO - 10.1371/journal.pone.0143288
M3 - Article
C2 - 26599441
AN - SCOPUS:84957869054
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 11
M1 - e0143288
ER -