The IBD5 (MIM# 606348) chromosomal region on 5q31 contains the genes for organic cation transporters, OCTN1 and OCTN2, and has been associated with susceptibility to adult onset CD. While several studies argue that OCTN1 and OCTN2 are the causal genes, others fail to replicate these results.
From the Canterbury Inflammatory Bowel Disease Project, 388 CD, 405 UC, and 27 indeterminate colitis (IC) participants were genotyped for functional SNPs in OCTN1, OCTN2, and IL4 genes, in comparison with 370 controls. TaqMan® technologies were used to genotype IL4 rs2243250, OCTN1 rs1050152, and OCTN2 rs2631367 according to standard methodologies. The frequencies of variant SNPs in the control population were compared with frequencies in cases, where phenotype data for IBD was classed according to the Montreal classification.
For those individuals carrying only the variant allele in IL4 or OCTN1, despite trends towards increased risk of developing IBD, there were not statistically significant differences. There were no other specific effects of this allele in the location of CD, behaviour of UC or CD, or any other differences between controls and patient subgroups in this population group. However, carrying the variant OCTN2 rs2631367 allele significantly increased the risk of ileocolonic CD (OR=1.42, 95% CI=1.02-1.97, p<0.05).
Despite earlier reports suggesting that OCTN1 and OCTN2 variants might provide important risk factors for IBD in New Zealand, this larger population-based study failed to confirm the earlier data. SNPs in the IL4 gene did not affect the analysis. We suggest the possibility that strong effects for these variants in these genes seen in some studies could imply gene-environment interactions.
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