The expression of TAP1 candidate gene, but not its polymorphism and methylation, is associated with colonic polyp formation in a porcine model of human familial adenomatous polyposis.

In humans, the dysfunction of the adenomatous polyposis coli (APC) gene causes hereditary familial adenomatous polyposis (FAP) and increased risk of colorectal cancer (CRC). The severity of polyposis varies between individuals, but genetic basis for this is in large part unknown. This variability also occurs in our porcine model of FAP, based on an APC1311 mutation (orthologous to human APC1309 ). Since loss of TAP1 function can lead to CRC in humans, we searched for germline polymorphisms in APC1311/+ pigs with low (LP) and high (HP) levels of polyposis, as well as in wild-type pigs representing six breeds and a commercial line. The distribution of 40 identified polymorphic variants was similar in the LP and HP pigs. In contrast, the TAP1 transcript level was significantly higher in normal colon mucosa of HP pigs than in LP pigs. Moreover, six SNPs showed significant effects on TAP1 promoter activity, but no correlation with severity of polyposis was observed. Analysis of DNA methylation in the promoter region showed that one CpG site differed significantly between LP and HP pigs. We conclude that TAP1 genotype may not itself be associated with polyposis, but our findings concerning its expression suggest a role in the development of polyps.