HFE genetic variability and risk of alcoholic liver disease: A meta-analysis

Abstract

Studies examining the association of hemochromatosis (HFE) gene polymorphisms and susceptibility to alcoholic liver disease (ALD) yielded inconsistent results. Thus, we performed a metaanalysis to investigate whether the variations in HFE gene increase the risk of ALD. The studies published up to Feb. 2014 were identified by searching PubMed/MEDLINE, ISI Web of Science, EMBASE and China National Knowledge Infrastructure databases, which was complemented by screening the references of the retrieved studies. For all genotypes and alleles, the odds ratios (ORs) with 95% confidence intervals (CIs) according to the heterogeneity were pooled using fixed-effect model. Sixteen studies with 1933 cases and 9874 controls were included for this meta-analysis. C282Y/C282Y, C282Y/wild type, H63D/wild type and C282Y/H63D were found not to be associated with susceptibility to ALD, but increased risk of H63D/H63D (OR: 1.52, 95% CI: 1.05-2.22, P=0.029) was observed for ALD when compared to total control. Comparison of ALD patients with alcoholics without liver damage revealed a significant association of D allele, as well as a marginal association of H63D/wild type with ALD, while H63D/H63D was not significantly associated with ALD although increased value of OR was obtained. The presence of Y allele and other genotypes yielded insignificant findings when ALD patients were compared with alcoholics without liver damage. No evident publication bias or significant heterogeneity among studies was detected in this meta-analysis. In conclusion, our metaanalysis showed a marginal higher prevalence of H63D variant in ALD but did not support an increased risk of C282Y mutation.

Keywords: alcoholic liver disease; hemochromatosis gene; meta-analysis; polymorphisms.