Z Gastroenterol 2007; 45 - A2_18
DOI: 10.1055/s-2007-967808

Lithogenic dyslipidemia and ABCG5/ABCG8 gene polymorphisms: a study in 121 siblings with gallstones

F Grünhage 1, S Tirziu 2, A Ciocan 2, S Bel 3, H Keppeler 1, F Lammert 4, M Acalovski 2
  • 1Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn, Bonn
  • 23rd Medical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romnania
  • 3Institute of Biology, Babes-Bolyai University, Cluj-Napoca, Romania
  • 4Medizinische Klinik und Poliklinik I, Universität Bonn, Bonn

Background

Most epidemiological surveys confirm the association of low HDL-cholesterol levels and hypertriglyceridemia with cholesterol gallstone disease. The recently identified hepatobiliary cholesterol transporter is a heterodimeric complex of two proteins which are encoded by the ABCG5 and ABCG8 genes. As recently shown, common genetic variants in this cholesterol transporter account for the variability of plasma cholesterol levels in a reference population (Berge et al. 2002. J Lipid Research; 43: 486–494). Hence both genes represent candidate genes for cholesterol gallstone formation. The present study aimed to evaluate plasma lipid levels in affected siblings with gallstones in relation to common ABCG5/ABCG8 gene polymorphisms.

Methods

Plasma levels of cholesterol, HDL-cholesterol and triglycerides were assessed in 121 siblings from Romania with gallstones (females / males=104 / 17, mean age 54.0±11.7 yrs, mean BMI 28.3±5.1kg/m2). Four non-synonymous sequence variants (SNPs) in the ABCG8 gene (rs11887534 (D19H); rs4148211 (Y54C), rs4148217 (T400K), rs6544718 (A632V)) and one in the ABCG5 gene (rs6720173 (Q604E)) were genotyped by allelic discrimination using 5rsquor; nuclease assays. The correlations of plasma lipid levels in the sibling pairs were calculated with Pearsonrsquor;s and Spearmanrsquor;s correlation coefficients. Student's t test was used to compare plasma lipid levels in the carriers of ABCG5 and ABCG8 SNPs divided into two groups: (1) homozygous carriers of the common allele and (2) heterozygotes or homozygous for the minor allele.

Results

Plasma cholesterol (r=0.553) and triglyceride levels correlated significantly (r=0.431) between members of the sibling pairs with gallstones. The correlation was independent of age and BMI. Triglyceride and cholesterol levels were significantly higher and HDL-cholesterol levels were lower in carriers of the common alleles as compared to carriers of the rare alleles for the ABCG5 Q604E polymorphism. However, no association was found for the other SNPs.

Conclusion

Our results suggest a possible influence of ABCG5/ABCG8 variants on plasma lipid levels in affected sib pairs with gallstones