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Aliment Pharmacol Ther. 2007 Nov 15;26(10):1325-32. Epub 2007 Sep 24.

Evidence of allelic heterogeneity for associations between the NOD2/CARD15 gene and ulcerative colitis among North Indians.

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1
Department of Genetics, University of Delhi, South Campus, New Delhi, India.

Abstract

BACKGROUND:

Three common disease susceptibility variants in the NOD2 gene are associated with inflammatory bowel disease in Caucasians, but not in Asians. Aim To screen for NOD2 variants and examine susceptibility for inflammatory bowel disease in North Indians.

METHODS:

A case-control study was carried out in Punjab, India. Confirmed cases of ulcerative colitis and Crohn's disease and healthy controls matched for age (+/-10 years) and ethnicity were studied. Besides genotyping the three disease susceptibility variants (SNP8, SNP12 and SNP13), all 12 exons were resequenced to determine other potential single nucleotide polymorphisms.

RESULTS:

Two hundred and ninety-eight ulcerative colitis, 25 Crohn's disease and 262 controls were investigated. Median age (range) at diagnosis was 39 (7-78) years for ulcerative colitis and 40 (32-58) years for Crohn's disease. All three disease susceptibility variants were either monomorphic or rare in the population. Sequencing (n = 30) revealed two single nucleotide polymorphisms: SNP5 (268 Pro/Ser) and rs2067085 (178 Ser/Ser). The frequency of SNP5 was higher among ulcerative colitis (17% vs. 12% in controls, P = 0.016) and Crohn's disease cases (20% vs. 12%, P = 0.28). SNP5 carriers had elevated risks for ulcerative colitis (OR = 1.72, 95% CI = 1.17-2.52, P = 0.005).

CONCLUSIONS:

The absence of known inflammatory bowel disease susceptibility variants and potential associations between SNP5 and ulcerative colitis in North Indians suggests the presence of allelic heterogeneity for ulcerative colitis susceptibility.

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