Original research

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

Adriana Zapata-Velandia^1,4 , San-San Ng^2,4 , Rebecca F Brennan¹ , Neal R Simonsen⁵ , Mariella Gastanaduy^1,4 , Jovanny Zabaleta^3,4 , Jennifer J Lentz² , Randall D Craver³ , Hernan Correa³ , Alberto Delgado³ , Angela L Pitts^2,4 , Jane R Himel^1,4 , John N Udall Jr¹ , Eberhard Schmidt-Sommerfeld¹ , Raynorda F Brown¹ , Grace B Athas³ , Bronya B Keats⁴ and Elizabeth E Mannick^1,4

¹Louisiana State University Department of Pediatrics, New Orleans, LA 70112, USA

²Louisiana State University Department of Genetics, New Orleans, LA 70112, USA

³Louisiana State University Department of Pathology, New Orleans, LA 70112, USA

⁴Stanley S. Scott Cancer Center, New Orleans, LA 70112, USA

⁵Louisiana State University School of Public Health, New Orleans, LA, 70112 USA

author email corresponding author email

Journal of Immune Based Therapies and Vaccines 2004, 2:6doi:10.1186/1476-8518-2-6

Published:	14 May 2004

Abstract

Background

Polymorphisms in several genes (NOD2, MDR1, SLC22A4) have been associated with susceptibility to Crohn's disease. Identification of the remaining Crohn's susceptibility genes is essential for the development of disease-specific targets for immunotherapy. Using gene expression analysis, we identified a differentially expressed gene on 5q33, the colony stimulating factor 1 receptor (CSF1R) gene, and hypothesized that it is a Crohn's susceptibility gene. The CSF1R gene is involved in monocyte to macrophage differentiation and in innate immunity.

Methods

Patients provided informed consent prior to entry into the study as approved by the Institutional Review Board at LSU Health Sciences Center. We performed forward and reverse sequencing of genomic DNA from 111 unrelated patients with Crohn's disease and 108 controls. We also stained paraffin-embedded, ileal and colonic tissue sections from patients with Crohn's disease and controls with a polyclonal antibody raised against the human CSF1R protein.

Results

A single nucleotide polymorphism (A2033T) near a Runx1 binding site in the eleventh intron of the colony stimulating factor 1 receptor was identified. The T allele of this single nucleotide polymorphism occurred in 27% of patients with Crohn's disease but in only 13% of controls (X² = 6.74, p < 0.01, odds ratio (O.R.) = 2.49, 1.23 < O.R. < 5.01). Using immunohistochemistry, positive staining with a polyclonal antibody to CSF1R was observed in the superficial epithelium of ileal and colonic tissue sections.

Conclusions

We conclude that the colony stimulating factor receptor 1 gene may be a susceptibility gene for Crohn's disease.