Multiple mucin genes polymorphisms are associated with gallstone disease in Chinese men

Background: Gallstone is a complex disease caused by multiple environmental and genetic factors. One of these is mucin glycoproteins. This case-control study aimed to investigate the association between single nucleotide polymorphisms (SNPs) at the MUC1-4 genes and gallstone.

Methods: The study included 475 cases and 941 controls. Eight tagging SNPs were selected: one at MUC1, two at MUC2, and five at MUC4. There was no available tagging SNP at MUC3. Genetic effects were initially evaluated by multivariate logistic regression. The combined effects from multiple genes were further evaluated, as well as the sex-specific effect. Permutation was used to correct for multiple testing.

Results: The genotypes were all in Hardy-Weinberg equilibrium. SNP rs7396030 at MUC2 yielded a p value of 0.03. Further sex-specific analysis showed significance solely with male subjects (p=0.005). Similarly, SNP rs4072037 at MUC1 was only significant (p=0.035) in males. The permutation empirical p values were 0.005 for rs7396030 and 0.02 for rs4072037. For males, the combined genetic effect yielded an OR of 4.68 (p=0.0008).

Conclusions: The SNPs at MUC1 and MUC2 are significantly associated with gallstone in men but not in women. These genes can work jointly to further increase susceptibility to gallstone in a Chinese population.