J. Hallion1, S. O’Brien1, C. Fiechter1, M. B. Ekman1, J. Burton1, M. Eichenberger1, S. Galandiuk1 1Price Institute of Surgical Research,University Of Louisville,Louisville, KENTUCKY, USA
Introduction: Crohn’s disease is a common inflammatory disorder of the gastrointestinal tract. It has a multifactorial etiology with immunological, environmental, and genetic factors. Phenotypically, Crohn’s disease was classified (Montreal Classification) using age of onset, disease location, and disease behavior. Single nucleotide polymorphisms (SNPs) are common single base pair genetic variants between individuals and are associated with disease phenotype in a number of diseases. Recent genome wide exploratory studies have identified SNPs that are associated with a stricturing phenotype in Crohn’s disease. The aim of this study was to determine if SNP allele frequencies truly correlate with stricturing Crohn’s disease phenotype in a mid-western Caucasian United States population.
Methods: Patients with Crohn’s disease were selected from a prospectively maintained university surgical digestive practice database. Blood samples were drawn during clinic appointments. Patients with stricturing (Montreal B2) and non-stricturing (Montreal B1) phenotypes were eligible for inclusion. Clinical data were extracted from an electronic database and patients were matched for gender and race. Genomic DNA was extracted from the blood sample, and 4 SNPs (NOD2 rs2066844 R702W, FUT2 rs601338, IL23-R rs1004819, ATG16L1 rs2241880 T300A) were assessed using a TaqMan genotyping assay.
Results: One hundred and sixty-three patients with Crohn’s disease were included in this study; 65% (106/163) were female. Age of onset (Montreal A) was equally distributed between the stricturing and non-stricturing groups (p=0.408). There was no difference in disease location (p=0.814), or the presence of upper GI disease (p=0.274) between the groups. There was no difference in allele frequency or genotype frequency between the stricturing and non-stricturing groups for FUT2, ATG16L1, or IL23-R (Table 1). The T allele (p=0.004) and the TT genotype (p=0.035) in the NOD2 R702W SNP were significantly associated with a non-stricturing phenotype.
Conclusion: We confirmed a significant association between a non-stricturing phenotype and the TT genotype and the T allele in the NOD2 R702W SNP. NOD2 is a well characterized gene that is involved in Crohn’s disease pathophysiology and the results of this study validate the results of large genome wide association studies in a United States population. Further study is required to determine if the NOD2 R702W T allele is a protective factor against stricturing disease.
