Despite our large sequencing approach, we could not identify protein altering variants in the genes HNF4A, ECM1, CDH1 and LAMB1 which could explain an impaired intestinal barrier function in UC.
Notably, genes implicated in mucosal barrier function (ECM1, CDH1, HNF4α, and laminin B1) confer risk of UC; furthermore, E-cadherin is the first genetic correlation between colorectal cancer and UC.
XRCC1 Arg399Gln and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 84 UC patients without neoplastic lesions, in relation to CIHM in the rectal mucosa of three candidate CpG loci (p14, p16, and CDH1) assessed by methylation-specific polymerase chain reaction.
Allelic association analysis showed that SNP rs6017342 in the HNF4α locus was strongly associated with UC (P = 1,04 × 10(-11) , odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.37-1.77) and SNP rs1728785 (CDH1) was associated with P = 0.01 (OR = 1.23, 95% CI = 1.05-1.44).
Sixty eight colorectal cancers (22 RER+ sporadic cancers, 32 RER- sporadic cancers and 14 ulcerative colitis associated cancers) were studied using immunohistochemistry and for allele loss at the HSECAD locus.