The association between aldehyde dehydrogenase gene (ALDH2) polymorphism and cognitive impairment among Chinese oldest old

Abstract

AbstractBackgroundAldehyde dehydrogenase 2 (ALDH2) is one of the aldehyde dehydrogenase isoforms responding for 3,4‐dihydroxyphenylglycolaldehyde metabolism and a common mutation in ALDH2 (rs671 AG or AA) causes the activity of ALDH2 to be reduced which was associated with Asian flush and series of cancers. Recent study suggested that carrying rs671 A allele and high intaking of alcohol will jointly increase the risk of Alzheimer disease in mice. Accordingly, we investigated the association between the ALDH2 RS671 genotype and cognitive impairment among Chinese oldest old.MethodWe used a genetic sub‐study of the Chinese Longitudinal Healthy Longevity Survey including 1949 participant aged over 90 years old. Mini‐Mental State Examination (MMSE) score was used to ascertain cognitive impairment at baseline, defined as MMSE score less than 18 out of 30. RS671 genotype was further categorized as non‐carrier (GG) and carriers (AG or AA). Multivariable logistics regression models were applied to examine the association between RS671 genotype and cognitive impairment.ResultAmong the participants, 76.2% were women and 36.0% were RS671 carriers, with a mean age of 100.7 (SD 3.29) years. The mean MMSE score was 16.4 (SD: 10.6) and 49.3% of the participants had cognitive impairment. Carrying RS671 mutation was associated with 26.1% higher odds (95% CI: 0.7%‐58.0%) of cognitive impairment. Significant interaction between RS671 genotype and fruit consumption (P=0.045) was observed. Carrying RS671 mutation was significantly associated with higher odds of cognitive impairment among those with low fruits consumption (OR=1.58, 95% CI 1.01‐2.51), but the significance was not significant in the group with high fruits consumption.ConclusionIn the Chinese oldest old, carrying ALDH2 RS671 mutation was associated with higher odds of cognitive impairment, and the association between RS671 genotype and cognitive impairment is more pronounced in those with low fruit consumption. No interaction between alcohol consumption and RS671 genotype was observed.