Polymorphism of CC chemokine receptors CCR2 and CCR5 in Crohn's disease

Crohn's disease (CD) is a chronic inflammatory disease of the intestine tha t is characterized by mononuclear cell infiltration and a predominant Th1 l ymphocyte response. We tested the hypothesis that CC chemokine receptors CC R2 and CCR5 might be important in the regulation of the intestinal immune r esponse in this disease, and we speculated that carriers of a defective 32 base pair deletion mutant of CCR5, CCR5 Delta 32, which results in a non-fu nctional receptor, might be protected from CD. Using polymerase chain react ion (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP) gene frequencies of CCR5 Delta 32 and of CCR2-641 (replacement of valine-64 by i soleucine in the CCR2 gene) in healthy controls (n = 346) and in CD patient s (n = 235) were determined. In CD patients, subgroup phenotypic analyses w ere performed according to the Vienna classification. The overall gene freq uency of CCR5 Delta 32 (9.8%) and CCR2-641 (7.6%) in CD patients did not de viate significantly from healthy controls (9.2 and 8.2%, respectively), nor did we observe a significant deviation from the predicted Hardy-Weinberg d istribution. No significant differences in the CD phenotype classification for the different CCR5 and CCR2 alleles were observed, except for a trend t o disease sparing of the upper gastrointestinal tract (carrier frequency 0 versus 19.6%, Delta = 1 9.6%, P = 0.079) as well as a more stricturing dise ase behaviour (23.5 versus 16.2%, Delta = 7.3%, P = 0.136) in carriers of t he mutant CCR5 Delta 32 allele. These results indicate that the different C CR5 but not CCR2 alleles may influence disease behaviour and thereby contri bute to the observed heterogeneity of CD. However, the associations observe d are limited and await replication in other datasets. CCR2 and CCR5 polymo rphisms are unlikely to be important determinants of overall disease suscep tibility. (C) 2001 Elsevier Science B.V. All rights reserved.