title: Association of apolipoprotein A1-C3 gene cluster polymorphisms with gallstone disease.
abstract: BACKGROUND
  Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Genetics, Sanjay Gandhi Postgraduate Institue of Medical Sciences, Lucknow, India.
authors.forename: Manjusha
authors.initials: M
authors.lastname: Dixit
authors.forename: Gourdas
authors.initials: G
authors.lastname: Choudhuri
authors.forename: Rajan
authors.initials: R
authors.lastname: Saxena
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics*; D053305:Apolipoprotein C-III / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D042882:Gallstones / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III