Gastroduodenal Crohn's Disease Is Associated With NOD2/CARD15Gene Polymorphisms, Particularly L1007PHomozygosity

Abstract

Limited data exist on the specific association between gastroduodenal Crohn's disease (GDCD) and NOD2/CARD15gene polymorphisms. The aim of this study was to assess the association between NOD2polymorphisms and GDCD, and to assess the specific association between each of the 3 major allelic variants G908R, L1007P, and R702Wand the clinical features of Crohn's disease. We retrospectively reviewed the records of 202 patients with confirmed Crohn's disease and complete data was performed. Seventy-one patients (35%) had at least 1 allelic variant: 55 had 1 variant, 4 were homozygous for L1007fs, 2 homozygous for R702W, and 10 were compound heterozygous. Eighteen patients with confirmed GDCD were identified; 10 (56%) had wild type, 4 (22%) had 1 variant, and 4 (22%) had 2 allelic variants (2 were L1007Phomozygous and 2 compound heterozygous). Compared to patients without gastroduodenal involvement, those with GDCD were more likely to have 2 allelic variants (22% vs. 6%; odds ratio [OR] 2.7; 95% confidence interval [CI] 1.6–7.3) and to be homozygous for L1007P(11% vs. 1%; OR 5.2; 95% CI 2.5–9.4). G908Rheterozygosity was associated with ileal involvement (OR 1.4; 95% CI 1.1–2.9) and smoking habits (OR 2.4; 95% CI 1.2–3.8), whereas L1007Phomozygosity was associated with GDCD (OR 5.8; 95% CI 2.6–10.8). L1007Pvariation was associated with younger age at diagnosis as well. There was no specific association between R702Whomo- or heterozygosity and any of the characteristics examined. In conclusion, GDCD is associated with double dose of the NOD2/CARD15gene variants, particularly L1007Phomozygosity. There is evidence of specific variant-phenotype associations. G908Rheterozygosity is associated with ileal involvement and smoking, whereas L1007Phomozygosity is strongly associated with GDCD and younger age at diagnosis.