Association Study of SLCO1B3 and ABCC3 Genetic Variants in Gallstone Disease.

Bolesław Banach,Zygmunt Juzyszyn,Andrzej Pawlik,Mateusz Kurzawski,Tomasz Sroczynski,Andrzej Modrzejewski

doi:10.3390/genes13030512

Abstract

There is growing evidence that gallstone formation may be genetically determined. Recent studies have shown that polymorphism of genes encoding proteins involved in bile acid transport may be associated with the risk of gallstone disease. The aim of this study was to investigate the association between SLCO1B3 (rs4149117:G>T, rs7311358:A>G) and ABCC3 (rs4793665:T>C, rs11568591:G>A) genetic variants and susceptibility to cholesterol gallstone disease, as well as gallstone composition. The study included 317 patients suffering from cholelithiasis who underwent cholecystostomy and 249 controls with no evidence of stones, confirmed by ultrasound examination. There were no statistically significant differences in the distribution of studied gene polymorphisms between patients with gallstone disease and healthy controls. No significant associations were observed between studied genotypes and the content of analyzed gallstone components: total cholesterol, bilirubin, CaCO3, nor the total bile acids. There was also no association between bile acid content in gallstones and the polymorphisms studied. The results of this study suggest that polymorphisms of SLCO1B3 and ABCC3 genes are not a valuable marker of gallstone disease susceptibility and do not influence gallstone composition.

Highlights

The aim of this study was to investigate the association between SLCO1B3 and ABCC3 genetic variants and susceptibility to cholesterol gallstone disease, as well as gallstone composition
We decided to analyze in that context the potential role of functional polymorphism in two genes expressed in basolateral membrane of hepatocytes: SLCO1B3 and ABCC3
It can be expected that the functional polymorphisms of the transporters studied may affect their substrates, i.e., the bile acid content in the stones

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Cholelithiasis is one of the most common gastroenterological illnesses. In Europe and the United States, it affects 10 to over 20% of the population [1]. There are many identified environmental risk factors for gallstone disease (GSD). The most important are: age, gender, diet, obesity, hyperlipidemia, diabetes, elevated estrogen levels, pregnancy, liver cirrhosis and hemolytic disease [2]. The role of genetic factors in the disease pathogenesis is widely discussed. Observations proving the occurrence of GSD in humans of different geographic regions, different ethnic groups, within families, and in monozygous and heterozygous twins directly indicate the presence of genetic conditions. The contribution of genetic factors in the pathogenesis of GSD is estimated to be from about 20% to over

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