Evaluation of the interleukin-23 receptor gene coding variant R381Q in pediatric and adult Crohn disease.
BACKGROUND
Pediatric-onset Crohn disease (CD) may differ in genotype or phenotype from adult-onset CD. Genome-wide screening recently identified a protective mutation (R381Q) in the interleukin-23 (IL-23) receptor gene located on chromosome 1. The aims of our study were to evaluate whether this mutation is associated with CD in our population and to find whether it may have an impact on age of onset or a specific location phenotype in a pediatric- and adult-onset CD population.


METHODS
A total of 438 individuals (143 with pediatric-onset CD [age <18 years], 139 with adult-onset CD, and 157 control subjects) evaluated for age at onset and disease location were genotyped for the R381Q mutation in the IL-23 receptor gene by pyrosequencing.


RESULTS
Mutant allele incidences were 5.7% in the normal cohort and only 2.28% in the CD cohort (P = 0.01). Carriers were found to constitute 8.9% of the normal cohort and only 4.6% of the CD cohort (P = 0.029). Homozygotes were found in only the control cohort. The mean age of onset for all of the patients with the mutation (including both age groups) was 17.8 +/- 6.1 years versus 21.3 +/- 12.4 years for patients without the mutation (P =0.08). The mutation was not associated with differences in sex, site of disease, or ethnicity. We did not find evidence of allelic interaction with CARD15.


CONCLUSIONS
We confirmed the findings that the IL-23 receptor gene coding variant allele R381Q appears to decrease susceptibility to CD in an Israeli Jewish population. We found a trend toward earlier age of onset, but no interactions with CARD15 or modifying effect on disease location.
Leshinsky-Silver
Esther
E
Molecular Genetics Laboratory, Holon, Israel. leshinsky@wolfson.health.gov.il
Karban
Amir
A
Dalal
Ilan
I
Eliakim
Rami
R
Shirin
Haim
H
Tzofi
Tzipi
T
Boaz
Mona
M
Levine
Arie
A
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics*
C515500:IL23R protein, human; D020033:Protein Isoforms; D018123:Receptors, Interleukin