Haplotype analysis of signal peptide (insertion/deletion) and XbaI polymorphisms of the APOB gene in gallbladder cancer.
2007
Purpose: The incidence of gallbladder cancer (GBC) is usually paralleled by the prevalence of gallstone disease, and genes of cholesterol metabolism have been implicated in gallstone disease. The XbaI and insertion/deletion (ins/del) polymorphism of Apolipoprotein B (APOB) appears to influence cholesterol homoeostasis and possibly risk for gallstone disease. We examined the effect of these polymorphisms individually as well as their haplotypes on GBC and gallstone patients in North Indian population.
Methods: The study comprises 123 consecutive cases of proven GBC, 172 cases of gallstone and 232 healthy subjects of similar age and sex. The genomic DNA was extracted from peripheral blood leucocytes and genotyping was performed using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism.
Results: In a case–control study, APOB XbaI and ins/del polymorphisms were not significantly associated with risk of GBC. Using the expectation maximization algorithm, four haplotypes were obtained, and haplotype X+,D was found to be significantly higher in GBC patients without stone in comparison with healthy subjects [odds ratio (OR) 2.9, 95% confidence interval 1.2–6.6 P=0.012].
Conclusions: The X+,D haplotype of APOB is associated with increased risk for development of GBC and the risk is not modified in the presence of gallstones.
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