Polymorphisms of MRP2 ( ABCC2) are associated with susceptibility to nonalcoholic fatty liver disease

We hypothesized that ABCC2 gene variants may contribute to susceptibility to nonalcoholic fatty liver disease (NAFLD). Additionally, we tested the hypothesis of a relation between gene variants and disease severity. The study involved 167 individuals: 109 consecutively presenting unrelated patients with features of NAFLD and different stages of disease severity, and a group of 58 healthy individuals. Four tag single-nucleotide polymorphisms (SNPs; rs717620 A/G, rs2756105 C/T, rs2002042 C/T and rs3740066 A/G) representing 46 polymorphic sites ( r 2>.8) were genotyped. Furthermore, two additional SNPs (rs17222723 A/T and rs8187710 G/A) were included. On univariate analysis, after multiple comparison correction by permutation tests, there were significant differences observed in the allele frequencies of rs17222723 and rs8187710 between healthy individuals and NAFLD patients (empirical P=.037 and .035, respectively). Allelic odds ratios [95% confidence interval] for rs17222723 and rs8187710 were 2.80 [1.11–7.04] and 2.80 [1.11–7.04], respectively. When we tested the hypothesis of a relation between gene variants and the clinical and histological spectra of NAFLD by multinomial regression analysis, a significant association was observed with the same markers: rs17222723 ( P=.0029) and rs8187710 ( P=.015). Our study suggests a potential role of ABCC2 in susceptibility to NAFLD and disease severity.