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 males 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-APOC3^SstI haplotypes also showed significant association while APOA1⁺⁸³-APOC3^SstI 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.