The common bile salt export pump (ABCB11) p.A444V variant is associated with BMI levels in the general population

Introduction: ABCB11 is a member of the ATP-binding cassette (ABC) transporters functioning as canalicular bile salt export pump. Mutations in the ABCB11 gene cause progressive familial intrahepatic cholestasis and polymorphisms in the G6PC2/ABCB11 region have been associated with fasting glucose levels in humans [1, 2]. The aim of the current study was to investigate if the common ABCB11 variant p.A444V known to affect the expression level of this hepatobiliary transporter is associated with higher BMI levels in the general population.

Materials and methods: We collected data including BMI from 277 German individuals (age 35–93 y.o., females n=149). The ABCB11 coding single nucleotide polymorphism (SNP) p.A444V (rs2287622) was genotyped using a PCR-based assay with 5'-nuclease and fluorescence detection. Statistical tests included regression analysis and ANOVA tests.

Results: In regression analysis, BMI was significantly correlated with the p.A444V variant (p=0.025). In total, CC, TC and TT genotypes were carried by 127, 102 and 48 individuals, respectively, with following mean BMI levels: CC=25.57, CT=25.53 and TT=27.55kg/m². Mean BMI levels were significantly higher in individuals carrying the TT genotype (p=0.0151).

Conclusions: The common ABCB11p.A444V variant predisposes to obesity in the general population. Especially individuals carrying the TT genotype suffer from high BMI levels as compared to subgroups with CC and CT genotypes. This phenomenon might be related to altered intestinal lipid absorption.

References:

[1] Strautnieks, S.S., et al., A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet, 1998. 20(3): p.233–8.

[2] Chen, W.M., et al., Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. J Clin Invest, 2008. 118(7): p.2620–8.