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

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 Al (APOAI) (-75 guanine [G] to adenine [A] and +83/84 M2(+1-), MspI) and apolipoprotein C3 (APOC3) (SstI) polymorphisms with gallstone disease. METHODS: MspI polymorphisms of the APOAI gene and Sstl poly, morphisms 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. APOAI +83 M2(+/-) and APOC3 Sstl polymorphisins 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% Cl 1.029 to 2.464), while A-M2(+)-SI was protective (P=0.002; OR 0.370, 95% Cl 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% Cl 1.774 to 5.674) for gallstone disease in males only. APOAI(-75)-APOC3(SstI) haplotypes also showed significant association while APOAI(+83)-APOC3(SstI) haplotypes showed no association with gallstone disease. CONCLUSIONS: The APOAI -75 G/A polymorphism is associated with gallstone disease and shows sex-specific differences. On the other hand, APOAI M2+1- and APOC3 Sstl polymorphisms may not be associated with gallstone disease. Haplotype analysis is a better predictor of risk for gallstone disease.