IL23R R381Q and ATG16L1 T300A are strongly associated with Crohn's disease in a study of New Zealand Caucasians with inflammatory bowel disease.
OBJECTIVE
Recently, separate genome-wide association analyses have identified nonsynonymous SNPs in IL23R and ATG16L1 (rs11209026; c1142G>A, R381Q, and rs2241880; c1338A>G, T300A, respectively) as strong candidate susceptibility factors for Crohn's disease (CD) in whites. The aim of our study was to test whether these SNPs are associated with CD in a population-based cohort of New Zealand Caucasian inflammatory bowel disease (IBD) patients.


METHODS
Allele frequencies of rs11209026 and rs2241880 were determined in 496 CD patients, 466 ulcerative colitis (UC) patients, and 591 controls. Distribution of the relevant alleles was compared between controls and IBD patients. rs11209026 and rs2241880 genotype distributions were examined both within IBD clinical subphenotypes and CARD15 genotypes.


RESULTS
rs11209026 and rs2241880 were both associated with CD (P valuers11209026=0.0026, OR 0.54, 95% CI 0.36-0.81; P valuers2241880=0.0001, OR 1.41, 95% CI 1.18-1.67). In addition, there was evidence for association of rs11209026 with UC (P value=0.037, OR 0.66, 95% CI 0.45-0.98). No significant association was observed between IL23R genotype or ATG16L1 genotype and IBD subphenotypes. IL23R was associated with CD and UC only in the absence of CARD15 mutations, whereas ATG16L1 was associated with CD in the presence and absence of CARD15 mutations.


CONCLUSIONS
We replicated the previously reported associations between CD and rs11209026 and rs2241880, confirming that IL23R and ATG16L1 are susceptibility loci for CD in the New Zealand population. We also provide further evidence for association of rs11209026 with UC and a report of an additive effect between IL23R and CARD15 genotypes in CD.
Roberts
Rebecca L
RL
Department of Pathology, University of Otago, Christchurch School of Medicine & Health Sciences, Christchurch, New Zealand.
Gearry
Richard B
RB
Hollis-Moffatt
Jade E
JE
Miller
Allison L
AL
Reid
Julia
J
Abkevich
Victor
V
Timms
Kirsten M
KM
Gutin
Alexander
A
Lanchbury
Jerry S
JS
Merriman
Tony R
TR
Barclay
Murray L
ML
Kennedy
Martin A
MA
D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008297:Male; D009520:New Zealand; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D044465:White People
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin