Association of alcohol dehydrogenase and aldehyde dehydrogenase 2 genetic polymorphisms with serum lipid profile: meta-analysis of mendelian randomisation studies

Background Alcohol dehydrogenase(ADH) and aldehyde dehydrogenase 2(ALDH2) are the key enzymes for alcohol metabolism. Several genetic studies have investigated the association between ADH and ALDH2 genetic polymorphisms and serum lipid profile(SLP), however, the results were inconsistent.Methods Fourteen articles involving 27,917 participants were included in this meta-analysis. Weighted mean difference(WMD) and 95% confidence intervals(CIs) were presented using random effects model. Publication bias was evaluated by funnel plot and Begg’s test. In addition, to further explore the heterogeneity, subgroup analysis were performed. Results Overall, there was no association between ADH genetic polymorphisms and SLP with no regard for drinking status. However, compared with ALDH2 wild homozygous genotype, ALDH2 mutant genotypes were associated with significant decrease in serum high density lipoprotein cholesterol(HDLC)(WMD-1.80 mg / d L, 95% CI-1.88 to-1.72, P < 0.001) and total cholesterol(TC) levels(WMD-1.10 mg / d L, 95% CI-1.59 to-0.62, P < 0.001), and significant increase in serum low density lipoprotein cholesterol(LDL-C) level(WMD 0.30 mg / d L, 95% CI 0.18 to 0.43, P < 0.001). Although there was no significant difference in serum triglyceride level in the overall population, subgroup analysis revealed that compared with ALDH2 * 1 wild homozygote, ALDH2 * 2 allele displayed a significant difference in serum triglyceride level between the female and male(female: WMD 1.69 mg / dl, 95% CI 1.08 to 2.30, P < 0.001; male:WMD-6.42 mg / d L, 95% CI-12.15 to-0.68, P = 0.028). Conclusion ADH genetic polymorphism has no association with SLP, regardless of sex category and drinking status. ALDH2 genetic polymorphism has slight association with HDL-C, LDL-C and TC levels and sex-specific association with serum triglyceride level.Whether or not the association between ADH2 genetic polymorphisms and SLP is resulted from alcohol consumption needs further investigation.