IL23RandIL12BSNPs and Haplotypes Strongly Associate with Crohn's Disease Risk in a New Zealand Population

Abstract

DNA samples from 339 Crohn's disease (CD) and 407 randomly selected controls from the Auckland (New Zealand) IBD project, were genotyped for five common single nucleotide polymorphisms inIL-23R(rs11805303, rs7517847, rs1343151, rs11209026, and rs10889677) and two inIL-12B(rs1363670 and rs6887695). While theIL-12Bvariants did not show an overall association and otherIL23Rvariants led to minor changes in the risk of CD, rs1343151 and/or rs7517847 variants in theIL-23Rgene strongly reduced the risk of developing CD at both allelic and genotype levels. A significantly decreased risk of first diagnosis of childhood CD was observed in individuals carrying the A allele of rs1343151, or between 17–40 y in individuals carrying the G allele in rs7517847 ofIL-23R. A significantly decreased risk of ileocolonic or structuring disease was observed in individuals carrying the A allele in either rs11209026 or rs1343151, or the G allele in rs7517847 ofIL-23R, and when such individuals did develop the disease, they were unlikely to require a bowel resection. Certain haplotypes very strongly modified risk. There was evidence for interactions ofIL-23Rvariants with theNOD2wild-type (d/d) genotype. Down-regulating the function of theIL-23Rgene may decrease CD risk in the normal population.