ABCB11 transporter gene variant p.A444V and gallstone susceptibility: a combined association and affected sib pair analysis

Introduction: Recent studies have identified common polymorphism of the hepatobiliary transporter gene ABCG8 (p.D19H) as a genetic risk factor for gallstones in humans^1,2. To further elucidate the role ABC transporters mutations in gallstones disease, we investigated a common variant of the bile salt export pump (ABCB11) in a combined association (case- control) and affected sib pair (ASP) analysis. Methods: Prospectively, we collected 235 individuals with gallstones (confirmed by ultrasound or cholecystectomy) from 108 families (age 24–80 years, 86% women, BMI 17–49kg/m²) and 260 gallstone-free controls (confirmed by ultrasound, age 21–78 years, 93% women, BMI 16–43kg/m²). Using PCR-based assays with 5'-nuclease and fluorescence detection (TaqMan), we genotyped the ABCB11 coding SNP p.A444V, which is known to affect transporter expression. We performed nonparametric linkage (NPL) analysis in affected sib pairs (ASPs) and association tests in cases and controls. Results: Allele frequencies were within Entrez SNP database ranges and no deviation from Hardy-Weinberg equilibrium was detected. However, neither allele and genotype distributions nor NPL scores provided evidence for association or linkage between the ABCB11 SNP and gallstones. Subsequent restriction of the association analysis to patients with BMI >30kg/m² did not reveal an association with gallstones either. Conclusions: The common ABCB11 variant does not confer increased gallstone risk in the general population. These findings are in line with a recent association study in the Popgen cohort in Northern Germany³.

Literatur: 1. Buch S., Schafmayer C., Becker C. et al. Nature Genetics. 2007;39(8):995-9. 2. Grünhage F., Acalovschi M., Tirziu S. et al. Hepatology. 2007;46(3):793-801. 3. Schafmayer C., Tepel J., Franke A. et al. Hepatology. 2006;44(3):650-7.

ABCB11 - SNPs - gallstones