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Genetic association found between uveitis, ankylosing spondylitis and IBD
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Overlapping but distinct genetic susceptibility loci were seen in patients with ankylosing spondylitis and acute anterior uveitis, as well as in patients with inflammatory bowel disease with two interleukins.
After applying quality control measures, genotyping was performed on 1,731 samples from patients with ankylosing spondylitis (AS), 238 samples from patients with primary acute anterior uveitis (AAU), 1,199 patients with both AAU and AS and from 9,564 healthy control participants. All patients were of European descent, and control participant genotypes were from the 1958 British Birth Cohort and the U.K. National Blood Transfusion Service.
Genotyping was performed on an Illumina Immunochip micro-array and intensity data were processed and normalized with Illumina GenomeStudio software, then clustered with optiCall.
Two analyses were performed. In the first, patients with both AAU and AS were compared with patients with AS alone. A second analysis compared all patients with AAU with control participants. The healthy control groups was randomly divided into two subgroups to match the AS and AAU groups.
Analysis was completed using two models. In model 1, all single-nucleotide polymorphisms (SNPs) associated with AAU in the analysis of all patients with AAU were compared with healthy control participants, and all SNPs associated with AS from the recently published International Genome-wide Association Study Immunochip data were assessed in the models. Model 1 included the SNP and principal components, and model 2 included HLA–B27 dose as a model covariate to reflect the previously studied interaction between ERAP1 SNPs and HLA–B27 in AS.
Detailed analysis showed that HLA-B27 was independently associated with risk for AAU, and major histocompatibility complex (MHC) class I and class II alleles other than HLA-B27 contributed to susceptibility for AAU, according to the researchers.
HLA-B27 was carried by 91.2% of patients with AS and comorbid AAU, in 80.6% of patients with AS without AAU, and in 63.9% of the small cohort of patients with AAU with unknown AS status.
Patients without AAU but with AS and comorbid irritable bowel disease (IBD) had lower expression of HLA-B27, and substantially fewer patients with IBD developed AAU, suggesting the allele offers relative protection against AAU, according to the researchers.
Additionally, the researchers found that the intergenic region chromosome 21q22 and ANTXR2 showed effect in patients with AS without AAU, and intergenic region chromosome 2p15 showed significant association in patients with AS only, suggesting genetic subgroups may exist among AS patients.
The IL18R1-IL1R1 SNP rs10197284 was shown to have strong linkage disequilibrium (LD) with SNPs previously reported to be associated with AAU and celiac disease and IBD, as well as in lesser LD to asthma, but not in AS. – by Shirley Pulawski
Disclosures: Robinson’s work was supported by the National Health and Medical Research Council of Australia and the University of Queensland Diamantina Institute. See the full study for a list of other authors’ disclosure information. Please see the full study for a list of all other authors’ relevant financial disclosures.
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