Association of apolipoprotein A1-C3 gene cluster polymorphisms with gallstone disease

Abstract

Introduction: Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease. Aim: To determine the association between apolipoprotein A1 (APOA1) (-75 guanine [G] to adenine [A] and +83/84 M2+/-, MspI) and apolipoprotein C3 (APOC3) (SstI) polymorphisms with gallstone disease. Methods: MspI polymorphisms of the APOA1 gene and SstI polymorphisms of APOC3 were analyzed in DNA samples of 214 gallstone patients and 322 age- and sex-matched healthy controls. All statistical analyses were performed using SPSS version 11.5 (SPSS, USA) and Arlequin version 2.0 (Arlequin, Switzerland). Results: The APOA1 -75 G/A polymorphism was significantly associated with gallstone disease. Patients with the GG genotype (P=0.015) and G allele carriers (P=0.004) had a significantly higher risk of gallstone disease (1.087-fold and 1.561-fold, respectively), whereas patients with AA genotypes (P=0.011) and A allele carriers (P=0.004) were protected (OR 0.230 and 0.641, respectively) against gallstone disease. APOA1 +83 M2+/- and APOC3 SstI polymorphisms were not associated with gallstone disease. Case-control analysis of haplotypes showed a significant association in mates only. G-M2+-S1 conferred risk for gallstone disease (P=0.036; OR 1.593, 95% CI 1.029 to 2.464), while A-M2+-S1 was protective (P=0.002; OR 0.370, 95% CI 0.197 to 0.695) against gallstone disease. In APOA1-75-APOA1+83 bilocus haplotypes, G-M2+ was associated (P=0.0001) with very high risk (OR 3.173, 95% CI 1.774 to 5.674) for gallstone disease in males only. APOA1-75-APOC3SstI haplotypes also showed significant association while APOA1+83-APOC3SstI haplotypes showed no association with gallstone disease. Conclusions: The APOA1-75 G/A polymorphism is associated with gallstone disease and shows sex-specific differences. On the other hand, APOA1 M2+/- and APOC3 SstI polymorphisms may not be associated with gallstone disease. Haplotype analysis is a better predictor of risk for gallstone disease. © 2007 Pulsus Group Inc. All rights reserved.