Association of Crohn's disease and ulcerative colitis with haplotypes of the MLH1 gene in Italian inflammatory bowel disease patients [2]

Crohn's disease (CD) and ulcerative colitis (UC), the two clinical entities comprising idiopathic inflammatory bowel disease (IBD), are complex disorders with a proven genetic predisposition. Several systematic genome wide searches for susceptibility genes in patients with IBD have reported linkage to specific regions of the genome. In particular, many replication studies, including a large international cooperative study and our own, have confirmed linkage to a locus on chromosome 16, named IBD1. Association of susceptibility to CD with allelic variants of NOD2, located in 16q12, has been recently reported. One of the worst complications of IBD, especially in UC, is the increased risk of colorectal cancer. Pokorny et alstudied three polymorphisms located inside or near the MLH1 gene, one of the DNA mismatch repair genes implicated in hereditary non-polyposis colon cancer (HNPCC), in a cohort of IBD patients. They found that specific MLH1 haplotypes were associated with the presence and family history of the disease in both CD and UC. Interestingly, markers from chromosome 3p21 located less than 10 cM away from the MLH1 gene showed evidence of linkage to IBD in a genome wide search. Following the initial report of Pokorny et al, we performed a case-control study with the aim of investigating the association of polymorphisms of the MLH1 gene with CD and UC in our population of Italian IBD patients.