Polymorphisms in the IBD5 Locus Are Associated With Crohn Disease in Pediatric Ashkenazi Jewish Patients

Abstract

Objectives: To analyze the IBD5 locus in a homogenous cohort of Ashkenazi Jewish (AJ) children with Crohn disease (CD). Patients and 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 >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 ¼ 0.017; odds ratio ¼ 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 ¼ 0.01; odds ratio ¼ 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. JPGN 48:531-537, 2009.

Association study betweenOCTN1functional haplotypes and Crohn's disease in a Korean population

“…In the case of OCTN, Peltekova et al [4] reported an association between the TC haplotype of OCTNs consisting of two genetic variants, OCTN1, L503F and OCTN2, g.-207G>C and susceptibility to CD. This finding was validated by several other association studies [14][15][16][17][18][19][20][21][22]. However, previous studies reported that these two variants are not found in Asian populations [17][18][19].…”

Two independent genetic factors responsible for the associations of the IBD5 locus with Crohnʼs disease in the Czech population

“…Peltekova et al 20 had shown that haplotypes consisting of at least one of the p.503Phe or c.-207C alleles on the nonrisk-associated IBD5 background (defined by IGR2078a_1) were more frequent in patients compared to controls, and based on this finding and functional studies, these variants in SLC22A4 and SLC22A5 genes were proposed to be causal. Similar to several previous studies, 21,22,29,[39][40][41] we did not confirm this finding; the power to detect the associations was, however, borderline. In our dataset, neither variants in SLC22A4 and SLC22A5 were associated with CD independently of IGR2063b_1 as the strongest associated SNP within IBD5.…”

The vesicle-associated function of NOD2 as a link between Crohn’s disease and mycobacterial infection

“…Indeed, genetic polymorphisms of polyspecific organic cation transporters OCTN1/2, translocating cytoplasmic serotonin through the cytoplasmic membrane, are among the CD predisposition factors [ 85 , 86 ]. Moreover, the CD-associated OCTN1 and NOD2 gene polymorphisms are additive for CD development [ 87 ].…”