IL-10R polymorphisms are associated with very-early-onset ulcerative colitis
Inflammatory Bowel Disease, 05/22/2012
Moran CJ et al. – The authors identified IL10RA polymorphisms that confer risk for developing very–early–onset (VEO)–UC. Additionally, they identified the first splice site mutation in IL10RA resulting in infantile–onset inflammatory bowel disease (IBD). This study expands the phenotype of IL10RA polymorphisms to include both severe arthritis and VEO–UC.Methods
- Candidate–gene analysis of IL10RA and IL10RB was performed after initial sequencing of an infantile onset–IBD patient identified a novel homozygous mutation.
- The discovery cohort included 188 EO–IBD subjects and 188 healthy subjects.
- Polymorphisms associated with IBD in the discovery cohort were genotyped in an independent validation cohort of 422 EO–IBD subjects and 480 healthy subjects.
- The authors identified a homozygous, splice–site point mutation in IL10RA in an infantile–onset IBD patient causing a premature stop codon (P206X) and IL–10 insensitivity.
- IL10RA and IL10RB sequencing in the discovery cohort identified five IL10RA polymorphisms associated with ulcerative colitis (UC) and two IL10RB polymorphisms associated with Crohn's disease (CD).
- Of these polymorphisms, two IL10RA single nucleotide polymorphisms, rs2228054 and rs2228055, were associated with VEO–UC in the discovery cohort and replicated in an independent validation cohort (odds ratio [OR] 3.08, combined P = 2 × 10–4; and OR 2.93, P = 6 × 10–4, respectively).