Polymorphisms in the IBD5 locus are associated with Crohn disease in pediatric Ashkenazi Jewish patients.
OBJECTIVE
To analyze the IBD5 locus in a homogenous cohort of Ashkenazi Jewish (AJ) children with Crohn disease (CD).


METHODS
A total of 83 AJ children with CD and 73 AJ healthy controls were studied. Genotyping for single nucleotide polymorphisms (SNPs) including OCTN1 (SLC22A4; 1672C-->T), OCTN2 (SLC22A5; 207G-->C), IGR2096, IGR2198, and IGR2230 genes was performed using the TaqMan system. NOD2/CARD15 variants also were typed using established methods.


RESULTS
All IBD5 SNPs tested were in linkage disequilibrium (D'>0.8), and showed significant association with CD in our cohort of AJ children. The IGR2096 SNP, which is not located within the same linkage disequilibrium block as the OCTN1 and 2 SNPs, showed an even stronger association with CD (P = 0.017; odds ratio = 1.7). Patients with CD who had the OCTN1 susceptibility allele were more likely to carry 1 of the 3 NOD2/CARD15 SNPs tested (P = 0.01; odds ratio = 4.8).


CONCLUSIONS
We have demonstrated a significant association between the IBD5 locus and CD in a homogenous cohort of pediatric AJ patients. Due to the tight linkage disequilibrium in the region, it is not possible to identify the causative IBD5 variant. Future functional studies will ultimately reveal the causative gene variant at this locus.
Tomer
Gitit
G
Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2010, Cincinnati, OH 45229, USA. gitit.tomer@cchmc.org
Wetzler
Graciela
G
Keddache
Mehdi
M
Denson
Lee A
LA
D048868:Adaptor Proteins, Signal Transducing; D002648:Child; D002895:Chromosomes, Human, Pair 5; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D027981:Symporters; D020691:rab GTP-Binding Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D027701:Organic Cation Transport Proteins; C120704:RPH3AL protein, human; C109807:SLC22A4 protein, human; D027981:Symporters; D020691:rab GTP-Binding Proteins