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Canadian Journal of Gastroenterology
Volume 21, Issue 9, Pages 569-575
Original Article

Association of Apolipoprotein A1-C3 Gene Cluster Polymorphisms with Gallstone Disease

Manjusha Dixit,1 Gourdas Choudhuri,2 Rajan Saxena,3 and Balraj Mittal1

1Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
2Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
3Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Received 5 April 2006; Accepted 22 October 2006

Copyright © 2007 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-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.