Colony-stimulating factor-1 receptor gene polymorphisms and Crohn’s disease

Abstract

Dear Editor: Zapata-Velandia et al. identified a single nucleotide polymorphism (A2033T) in an intron in the gene (CSF1R) encoding colony-stimulating factor-1 receptor (CSF1R), and revealed that the latter polymorphism was more common in American Crohn’s disease (CD) patients than in healthy controls, suggesting that CSF1R is a susceptibility gene for CD [Zapata-Velandia et al. (2004) Association of the T allele of an intronic single nucleotide polymorphism in the colony-stimulating factor 1 receptor with Crohn’s disease: a case-control study. J Immune Based Ther Vaccines 2:6]. CSF1R (OMIM 164770) is a receptor tyrosine kinase expressed in the superficial epithelium of the ileum and colon, which stimulates the proliferation, differentiation, and survival of monocytes, and macrophages. We examined the association between CSF1R and CD in New Zealand by genotyping the A2033T polymorphism in the eleventh intron of CSF1R. A total of 182 Caucasian CD patients and 188 ethnicallymatched control subjects were genotyped by PCR-RFLP analysis using the primer set described by ZapataVelandia et al. Statistical analysis was performed using the Chi-square or Fisher’s exact test. There was no significant difference in the genotype, allele, and carriage frequencies of the CSF1R 2033T polymorphism in controls vs CD patients [genotype AA 0.734 (n=138) vs 0.764 (n=139), AT 0.255 (n=48) vs 0.225 (n=41), TT=0.011 (n=2) vs 0.011 (n=2), P=0.80; allele T 0.138 vs 0.124, P=0.55; carriage of T allele 0.266 vs 0.236, P=0.51), respectively]. There was no significant difference (P=0.35 and 0.72, respectively) in the CSF1R 2033T allele frequencies of patients who did (0.093) or did not (0.129) carry the 3020insC polymorphism in the CD susceptibility gene CARD15 in comparison to control subjects (0.138) [for genotyping of the CARD15 3020insC allele refer to Leung et al. (2005) Polymorphisms of CARD15/ NOD2 and CD14 genes in New Zealand Crohn’s disease patients. Immunol Cell Biol 83:498–503]. There was no evidence that any of the genotype distributions deviate from Hardy–Weinberg equilibrium. There was no significant difference in the allelic distribution of the 2033T polymorphism with respect to disease location, behavior, or need of surgery in 177 CD patients for whom clinical data was obtained. In summary, there was no evidence that the 2033T variant is a major risk factor for CD in New Zealand. Post priori power calculations in which E. Leung . J. Hong . P. Vishnu . G. W. Krissansen (*) Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand e-mail: gw.krissansen@auckland.ac.nz Tel.: +64-9-3737599 Fax: +64-9-3737674