The longitudinal effect of the aldehyde dehydrogenase 2*2 allele on the risk for nonalcoholic fatty liver disease.

Y Sasaki,J Saruwatari,K Morita,Y Ogata,K Oniki,T Watanabe,A Kajiwara,K Nakagawa,K Otake

doi:10.1038/nutd.2016.17

Abstract

Aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes and has a key role in protecting the liver. An elevated gamma-glutamyl transferase (GGT) level is related to oxidative stress and nonalcoholic fatty liver disease (NAFLD). We herein investigated the association between inactive ALDH2*2 allele (rs671) and the risk of NAFLD, including the relationship to the GGT level. A retrospective follow-up study (mean 5.4±1.1 years) was conducted among 341 Japanese health screening program participants. The receiver operating characteristic curve indicated that the GGT level predicted the development of NAFLD (area under the curve: 0.65, P<0.05) with a cutoff value of 25.5 IUl−1. The longitudinal risk of NAFLD was higher in the ALDH2*2 allele carriers than in the noncarriers (odds ratio (OR): 2.30, 95% confidence interval (CI): 1.21–4.40), and the risk was further increased among the *2 allele carriers with GGT values ⩾25.5 IUl−1 (OR: 4.28, 95% CI: 1.80–10.19). On the other hand, there were no significant changes in the subjects' body weight and body mass index during observation period. The ALDH2*2 allele, in relation to the GGT level, may potentially be a novel risk factor for NAFLD.

Highlights

According to the receiver operating characteristic (ROC) curve, the gamma-glutamyl transferase (GGT) level at baseline was found to be a significant predictor of Nonalcoholic fatty liver disease (NAFLD), and the cutoff value was determined to be 25.5 IUl − 1
Among the 159 nondrinkers, the logistic regression models showed that the longitudinal risk of NAFLD increased in the Aldehyde dehydrogenase 2 (ALDH2)*2 allele carriers and in those with a GGT level of ⩾ 25.5 IUl − 1
To the best of our knowledge, this is the first report to show that the ALDH2*2 allele is associated with a risk for NAFLD in relation to an elevated GGT level

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease, which is recognized as a liver manifestation of metabolic syndrome, and it is a significant predictor of future coronary artery disease.[1,2,3] Oxidative stress is known to be of major importance in the development and progression of NAFLD.[1,2,3] Aldehyde dehydrogenase 2 (ALDH2) expressed in the liver detoxifies toxic aldehydes, such as acetaldehyde, 4-hydroxynonenal and malondialdehyde (derived from alcohol and/or generated by lipid peroxidation), and has a key role in protection from oxidative injury.[4,5] The ALDH2*1 and *2(rs671) alleles encode the active and inactive subunits of ALDH2, respectively, the latter of which determines an individual’s tolerance for alcohol consumption.[4,5] the active ALDH2*1/*1 genotype was identified to be a risk factor for alcoholism, alcohol-induced liver diseases and hypertension.[6,7] The inactive ALDH2*2 allele was identified to be a risk factor for coronary artery disease according to a meta-analysis of a genome-wide association study in East Asians.[8]. The present exploratory study aimed to investigate whether the ALDH2 rs[671] polymorphism could affect the risk for NAFLD using a longitudinal association analysis, while paying careful attention to the GGT level.

Results

Conclusion