Prevalence of ABCB4 polymorphisms in gallstone disease in han-Chinese population

ATP Binding Cassette Transporter A4 (ABCB4) is a sterol export pump that regulates excretion of biliary cholesterol. We tested association between ABCB4 polymorphisms and gallstone disease using meta-analysis. In a cross-sectional study, 296 subjects were recruited from a hospital-based population. Total of 171 subjects were diagnosed as gallstone disease by abdominal ultrasonography from three cohort studies. We evaluated prevalence of ABCG8 rs11887534 (D19H) as a positive control, and the ABCB4 rs1202283 and rs2230028 polymorphisms on Chinese population were screened by meta-analysis and genotyped using TaqMan® SNP assay. Stata/SE 11.0 software and random-effects model were used in meta-analyzing 3 cohort between study heterogeneity. Four studies including three cohorts were used for final meta-analysis. In allelic model, minor alleles of ABCB4 rs1202283 (OR = 0.41, 95% CI: 0.25-0.67, P<0.001) and of ABCB4 rs2230028 (OR = 0.12, 95% CI: 0.06-0.22, P = 0.001) were associated with an increased risk for gallstone disease in Europeans. Funnel plot and Egger's test suggested absence of publication bias. Concentration of total cholesterol, low-density lipoprotein cholesterol (LDLC) (P = 0.015) and high-density lipoprotein cholesterol (HDLC) (P = 0.028) were significantly higher in subjects with gallstones disease than controls. ABCB4 rs1202283 (heterozygote AG) (P<0.0001), rs2230028 (heterozygote CT) (P = 0.023) and ABCG8 rs11887534 (heterozygote CG) (P = 0.006) were significantly associated with gallstone disease in Chinese population. Genetic risk associated with ABCB4 rs2230028 (homozygote GG) polymorphism was dominated in asymptomatic gallstone disease (95% C.I.: 0.219-0.768; P = 0.005). In conclusion, carriers of ABCB4 rs1202283, rs2230028 are at an increased risk for gallstone disease, while ABCB4 rs2230028 is associated with asymptomatic gallstone disease.