ALDH2 rs671 Is Associated with Elevated FPG, Reduced Glucose Clearance and Hepatic Insulin Resistance in Japanese Men

Abstract

Context: A recent meta-analysis of genome-wide association studies data from East Asians identified aldehyde dehydrogenase 2 (ALDH2) rs671 as a susceptibility variant for type 2 diabetes in males. Objective: To investigate the association between ALDH2 rs671 and metabolic characteristics. Methods: We studied 94 nonobese, nondiabetic, Japanese men. Using a 2-step hyperinsulinemic-euglycemic clamp, we evaluated insulin sensitivity in muscle and liver. Intrahepatic lipid and fat distribution were measured using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively. We divided participants into a risk-carrying group with ALDH2 rs671 G/G (n=53) and a nonrisk-carrying group with ALDH2 rs671 G/A or A/A (n=41). Results: The risk-carrying group had significantly higher levels of alcohol consumption (18.4 [interquartile range, IQR, 10.4-48.9]) vs 12.1 (IQR, 1.3-29.0) g/day; P=.003), elevated fasting plasma glucose (FPG) (97.5±7.9 vs 93.5±6.2 mg/dL; P=.010), lower hepatic insulin sensitivity (61.7±20.5% vs 73.1±15.9%; P=.003), and lower fasting glucose clearance (0.84±0.8 dL·m-2·min-1 vs 0.87±0.09 dL·m-2·min-1; P=.047) than the nonrisk-carrying group, while insulin resistance in muscle and body fat distribution were similar. The single linear correlation analysis revealed significant correlations between alcohol consumption and hepatic insulin sensitivity (r=-0.262, P=.011), fasting glucose clearance (r=-0.370, P