Are plasma lipid levels related to ABCG5/ABCG8 polymorphisms? A preliminary study in siblings with gallstones

Acalovschi, Monica; Ciocan, Anca; Mostean, Ofelia; Tirziu, Simona; Chiorean, Erica; Keppeler, Hildegard; Schirin-Sokhan, Ramin; Lammert, Frank

doi:10.1016/j.ejim.2006.04.012

« Previous Next »European Journal of Internal Medicine
Volume 17, Issue 7 , Pages 490-494, November 2006

Are plasma lipid levels related to ABCG5/ABCG8 polymorphisms?:

A preliminary study in siblings with gallstones

Monica Acalovschi
- 3rd Medical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Romania
- Corresponding author. Monica Acalovschi, MD PhD, 3rd Medical Clinic, Dept. Gastroenterology, University of Medicine and Pharmacy, Str. Croitorilor no.19-23, 400162 Cluj-Napoca, Romania. Tel./fax: +40 264 433335.
Anca Ciocan
- 3rd Medical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Romania
Ofelia Mostean
- 3rd Medical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Romania
Simona Tirziu
- 3rd Medical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Romania
Erica Chiorean
- 3rd Medical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Romania
Hildegard Keppeler
- Department of Medicine I, University of Bonn, Germany
Ramin Schirin-Sokhan
- Department of Medicine I, University of Bonn, Germany
Frank Lammert
- Department of Medicine I, University of Bonn, Germany

Received 17 December 2005; received in revised form 5 April 2006; accepted 27 April 2006.

Abstract

Background

The role of ABCG5 and ABCG8 genes in the determination of plasma lipid levels is currently under intensive investigation. The aim of this study was to evaluate plasma lipid levels in sibling pairs with gallstones and to assess their correlation with common gene polymorphisms in the ABCG5/ABCG8 genes.

Methods

Plasma levels of cholesterol, HDL-cholesterol, and triglycerides were measured in 68 patients belonging to 34 sibling pairs with gallstones (affected sibling pairs, mean age 56.3 years) and in 68 gallstone carriers with stone-free siblings (age/gender-matched controls in a ratio of 2:1 with the index patients of the study group). Four and one non-synonymous sequence variants in ABCG8 and ABCG5 genes, respectively, were determined in the affected sibling pairs, employing allelic discrimination with 5′ nuclease assays.

Results

Plasma triglyceride levels were higher and HDL-cholesterol levels lower in the index patients than in controls. Plasma lipid levels were correlated in the members of the affected sibling pairs. Triglyceride levels were higher in carriers of the common alleles for ABCG5 Q604E and ABCG8 D19H sequence variants, and HDL-cholesterol was lower in carriers of the common alleles for ABCG5 Q604E than in carriers of the rare alleles.

Conclusions

The significantly different plasma lipid levels in siblings with gallstones versus controls, as well as the correlation of plasma lipids in affected sibling pairs, confirm the genetic influence in gallstone disease. Polymorphisms in ABCG5/ABCG8 genes might contribute to the genetic variation in plasma lipid levels and in cholesterol saturation of the bile.

Keywords: Polymorphism, ABCG5, ABCG8, Cholesterol, HDL-cholesterol, Triglycerides, Gallstones, Genetic determinants