Associations between NOD2, IRGM and ORMDL3 polymorphisms and pediatric-onset inflammatory bowel disease in the Lithuanian population

Abstract

Background and objective: Recent GWAS and meta-analyses have revealed about 200 susceptibility genes/loci for inflammatory bowel diseases (IBD). However, only a small number of studies were performed in early-onset IBD. The aim of this study was to assess the association between NOD2, IL23R, ATG16L1, IRGM, IL10, NKX2-3 and ORMDL3 variants and early-onset IBD.

Materials and methods: A total of 76 affected individuals (30 with Crohn's disease [CD] and 46 with ulcerative colitis [UC]) at the age of ≤17 years and 158 matched controls recruited in Lithuania were genotyped for the known genetic susceptibility variants in NOD2 (Arg702Trp (rs2066844), Gly908Arg (rs2066845) and Leu1007insC (rs2066847)), IL23R (rs11209026), ATG16L1 (rs2241880), IRGM (rs4958847), IL10 (rs3024505), NKX2-3 (rs11190140) and ORMDL3 (rs2872507) genes.

Results: Variants in NOD2 (Leu1007insC) and IRGM genes increased risk for CD (OR=6.56, 95% CI: 2.54-16.91, P=1.21×10^-5 and OR=2.32, 95% CI: 1.05-5.14, P=0.033; respectively); whereas a variant in ORMDL3 gene was strongly associated with UC (OR=1.99, 95% CI: 1.23-3.20, P=4.15×10^-3).

Conclusions: The results confirmed that polymorphisms in NOD2 (Leu1007insC) and IRGM genes are associated with increased risk of CD; whereas the ORMDL3 variant is associated with susceptibility to UC in the Lithuanian early-onset IBD population.

Keywords: Crohn's disease; Early onset; Inflammatory bowel diseases; Single nucleotide polymorphism; Ulcerative colitis.