We identified novel positive associations between CD and HLA-A*02:01 (odds ratio (OR)=1.64, P=0.016) and HLA-A*02:07 (OR=2.31, P=0.0067) and confirmed previously reported positive associations between CD and HLA-Cw*14:02 (OR=2.18, P=0.0021) and HLA-B*51:01 (OR=1.70, P=0.033).
We demonstrate that a MIR148A insertion/deletion polymorphism associates with its own expression levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3'UTR.
In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.
Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw*1202-B*5201-DRB1*1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10⁻³³; OR = 6.58), accounting for most of the associations observed in the GWAS.
The genotype 2DL2+/HLA-C lys(80)+ was also more common in controls (IBD: p = 0.005; UC: p = 0.01; CD: p = NS); as well as 2DL1+/HLA-C Asn(80)+ (IBD: p = 0.026; UC: p = NS;CD: p = NS).