Polymorphisms in Gene Predispose South Indians to Pigmentous Gallstones.

BACKGROUND/OBJECTIVES: Pigmentous gallstones occur in South Indians despite significant higher levels of circulating cholesterol. This study was conducted to identify the biochemical and/or genetic causes for the formation of pigmentous gallstones in this ethnic group.

METHODS

Plasma lipid profile, bile cholesterol, acids, and phospholipid levels were estimated in patients with gall stone disease and age, sex matched controls using standard protocols. Twenty-seven SNPs related to cholesterol and bilirubin metabolism pathway genes were genotyped in the study population using the Sequenom platform. An equilibrium phase diagram involving bile salt-phospholipid-cholesterol was generated to relate phenotype with the genotype.

RESULTS

There were no significant differences in the lipid profiles between the patients ( = 305) and controls ( = 177). Biliary cholesterol, acids, and phospholipids were significantly different between patients and controls. Single locus analysis revealed association of variants in , and genes with the disease; however when correction was applied as multiple testing was done, only one variant (rs6742078) in gene was found to be associated with gall stone disease. Equilibrium phase diagram suggested that few samples were in the crystal formation zone. The mutant, but not wild type or heterozygous genotype of SNPs (rs6742078 and rs887829) in gene, was associated with significantly higher levels of bilirubin.

CONCLUSIONS

Higher incidence of pigment stones in South Indians could be due to raised serum bilirubin levels that may be ascribed to variant in the gene involved in glucuronidation of free bilirubin.