title: Gastroduodenal Crohn's disease is associated with NOD2/CARD15 gene polymorphisms, particularly L1007P homozygosity.
abstract: Limited data exist on the specific association between gastroduodenal Crohn's disease (GDCD) and NOD2/CARD15 gene polymorphisms. The aim of this study was to assess the association between NOD2 polymorphisms and GDCD, and to assess the specific association between each of the 3 major allelic variants G908R, L1007P, and R702W and 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 L1007P homozygous 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). G908R heterozygosity 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 L1007P homozygosity was associated with GDCD (OR 5.8; 95% CI 2.6-10.8). L1007P variation was associated with younger age at diagnosis as well. There was no specific association between R702W homo- or heterozygosity and any of the characteristics examined. In conclusion, GDCD is associated with double dose of the NOD2/CARD15 gene variants, particularly L1007P homozygosity. There is evidence of specific variant-phenotype associations. G908R heterozygosity is associated with ileal involvement and smoking, whereas L1007P homozygosity is strongly associated with GDCD and younger age at diagnosis.
authors.affiliation: Department of Medicine, Division of Digestive Diseases and Nutrition, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536, USA. mardinih@uky.edu
authors.forename: Houssam E
authors.initials: HE
authors.lastname: Mardini
authors.forename: Kalvin J
authors.initials: KJ
authors.lastname: Gregory
authors.forename: Munira
authors.initials: M
authors.lastname: Nasser
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Selby
authors.forename: Razvan
authors.initials: R
authors.lastname: Arsenescu
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Winter
authors.forename: Willem J S
authors.initials: WJ
authors.lastname: de Villiers
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D003424:Crohn Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004378:Duodenal Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D015994:Incidence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011336:Probability; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D013272:Stomach Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein