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Updated: May 24, 2025

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Understanding the link between ALDH2 genotypes and diabetes.

Miaomiao Peng1,2, Ruikang Liu1,2,3, Jiaoyue Zhang1,2

  • 1Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Frontiers in Endocrinology
|March 6, 2025
PubMed
Summary

The ALDH2 GG genotype increases diabetes risk in East Asian men, especially with lower BMI. Adiposity, not alcohol, mediates this link, suggesting lifestyle changes for GG genotype carriers.

Keywords:
aldehyde dehydrogenasebody mass index (BMI)interaction effecttype 2 diabeteswaist circumference (WC)

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Area of Science:

  • Genetics and Genomics
  • Metabolic Diseases
  • Epidemiology

Background:

  • The association between aldehyde dehydrogenase-2 (ALDH2) rs671 and diabetes is debated, with unclear roles of alcohol and other factors.
  • This study investigates the ALDH2-diabetes link in a community cohort, considering confounding, mediating, and interacting factors.

Purpose of the Study:

  • To examine the association between ALDH2 rs671 and diabetes risk using standardized clinical criteria.
  • To systematically investigate potential confounding, mediating, and interacting factors in the ALDH2-diabetes relationship.

Main Methods:

  • Analysis of baseline data from 4,535 participants in the China Cardiometabolic Disease and Cancer Cohort Study (4C study).
  • Diabetes diagnosis based on fasting plasma glucose, 2-h postprandial glucose, HbA1c, or prior diagnosis.
  • Logistic and Cox regression models used to evaluate the ALDH2 rs671 and diabetes risk association, with mediation and interaction analyses.

Main Results:

  • The ALDH2 rs671 GA/AA genotype was linked to lower diabetes risk in men compared to GG genotype (OR = 0.751).
  • This protective effect was stronger in individuals with BMI < 24 (OR = 0.651), showing significant interaction (p=0.024).
  • Abdominal adiposity (30.4%) and BMI (18.9%) mediated the ALDH2-diabetes association, while alcohol consumption did not (p=0.56).

Conclusions:

  • East Asian men with the ALDH2 GG genotype face higher diabetes risk, particularly those with BMI < 24.
  • Adiposity, especially abdominal fat, acts as a mediator, not alcohol consumption.
  • Individuals with the GG genotype, even with normal BMI, may benefit from exercise and diet interventions targeting waist circumference.