Analysis of the CC chemokine receptor 5 (CCR5) delta-32 polymorphism in inflammatory bowel disease

The inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative c olitis (UC) are complex multifactorial traits involving both environmental and genetic factors. Recent studies have shown the important role of pro-in flammatory cytokines and chemokines, including RANTES, in IBD. RANTES is th e natural ligand for the CC-chemokine receptor 5 (CCR5). The chromosomal lo cation of the CCR5 gene on 3p21 coincides with an IBD-susceptibility locus identified by genome-wide scanning. A 32-bp deletion (Delta 32) in the CCR5 gene results in a nonfunctional receptor and is found with high frequency in Caucasians. In this study, we investigated the presence of the CCR5 Delt a 32 allele in a large cohort of IBD patients and in a healthy control popu lation Blood samples were obtained from 538 unselected IBD cases (433 unrel ated IBD patients: 289 CD, 1412 UC, 2 indeterminate colitis; 105 affected f irst-degree relatives) and 135 unaffected first-degree family members. Of t he IBD patients, 36% had familial IBD with at least two members being affec ted. There were no significant differences in the CCR5 Delta 32 mutation fr equency between IBD patients and healthy controls, nor between CD and UC pa tients. There was no correlation between the CCR5 Delta 32 genotype and the age at IBD-diagnosis, the frequency of surgical intervention, or disease l ocalization. Only the association between CCR5 Delta 32 homozygosity and th e presence of anal lesions in CD patients was statistically significant (P= 0.007). Analysis by the transmission/disequilibrium test showed no signific ant transmission distortion to the probands or their clinically silent sibl ings. Based on these results, it is unlikely that the CCR5 Delta 32 allele is an important marker for predisposition to IBD.