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 in IL-23R (rs11805303, rs7517847, rs1343151, rs11209026, and rs10889677) and two in IL-12B (rs1363670 and rs6887695). While the IL-12B variants did not show an overall association and other IL23R variants led to minor changes in the risk of CD, rs1343151 and/or rs7517847 variants in the IL-23R gene 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 of IL-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 of IL-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 of IL-23R variants with the NOD2 wild-type (d/d) genotype. Down-regulating the function of the IL-23R gene may decrease CD risk in the normal population.
Highlights
The inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC), are common gastrointestinal disorders in various countries, including New Zealand and parts of Europe
While the IL-12B variants did not show an overall association and other IL23R variants led to minor changes in the risk of CD, rs1343151 and/or rs7517847 variants in the interleukin-23 receptor (IL-23R) gene 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 of IL-23R
Summary
The inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC), are common gastrointestinal disorders in various countries, including New Zealand and parts of Europe. In New Zealand, it appears that their incidence is rising, and a geographically-based study in the Canterbury region in 2005 identified close to 1 in 250 people with the disease [1]. CD is increasing in New Zealand paediatric patients [2]. The symptoms can be debilitating, including abdominal cramping and bloody diarrhoea. An increasing number of studies are associating genes with susceptibility to the disease. Not all identified variants and genes show comparable risks in different countries [3]
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