rs10050860

This functional study demonstrates that ERAP1 gene expression is significantly influenced by spondyloarthritis (SpA)-associated SNP haplotypes in monocyte-derived dendritic cells and lymphoblastoid B cell lines. The rs17482078/rs10050860/rs30187 haplotype T/T/C (protective) correlates with lower ERAP1 expression, C/C/C (neutral) with intermediate levels, and C/C/T (susceptibility) with higher expression (P=0.001 and P=5.6×10⁻⁷ in discovery and replication cohorts). Protein expression and enzymatic activity follow similar patterns, suggesting ERAP1 polymorphisms affect peptide trimming capacity relevant to HLA-B27-mediated disease pathogenesis.

This study examined ankylosing spondylitis (AS) clinical features in 70 Orenburg region patients in relation to genetic and environmental factors. HLA-B27 was found in 92.86% of AS patients vs 5% of controls (OR=247.0, 95% CI 27.2–2245.0, p<0.001). Heterozygous genotypes at ERAP1 rs10050860 and rs17482078, combined with reduced zinc levels, were associated with functional impairment. IL23R rs11209026 heterozygous [G/A] genotype with chromium and nickel imbalance showed greatest impact on AS disease activity.

A case-control study of 150 Turkish ankylosing spondylitis (AS) patients and 150 healthy controls investigating 10 ERAP1 SNPs. The rs26653 SNP was significantly associated with AS susceptibility (OR 1.609, 95% CI 1.163-2.226; p = 0.004) with a population-attributable risk of 23.4%. The contribution of ERAP1 rs26653 to AS pathogenesis appeared independent from HLA-B27.

This meta-analysis of 9 case-control studies (8,530 AS patients and 12,449 controls) examined the association between ERAP1 polymorphisms and ankylosing spondylitis susceptibility. Six ERAP1 variants showed significant associations: rs27044 (OR 1.57, P<0.001), rs17482078 (OR 1.271, P<0.001), rs10050860 (OR 0.772, P=0.006), rs30187 (OR 1.348, P<0.001), rs2287987 (OR 0.746, P<0.001), and rs27037 (OR 1.257, P=0.001), while rs27434 showed no significant association (P=0.23). The findings support ERAP1's role in AS pathogenesis through peptide trimming for MHC class I presentation and cytokine receptor shedding.

This meta-analysis of six studies (4,594 AS cases and 3,971 controls) found significant associations between five ERAP1 polymorphisms and ankylosing spondylitis susceptibility, with rs27044 and rs30187 showing increased risk in both Europeans and Asians (OR = 1.333-1.554), while rs17482078, rs10050860, and rs2287987 showed protective effects in Europeans (OR = 0.708-0.726).

This confirmation study analyzes GWAS data from the CIDR familial Parkinson disease cohort (1048 cases, 895 controls) to validate previously reported associations between calpastatin (CAST) gene polymorphisms and Parkinson disease. The authors found a significant association between rs1559085 in CAST and PD (p=0.0167 after multiple comparison correction) with an allelic odds ratio of 1.43, confirming the association identified in the NINDS PD study and supporting CAST as a gene involved in PD etiology.

A genetic association study identified the ERAP2 gene as a novel preeclampsia susceptibility locus on chromosome 5q using SNP genotyping in Australian/New Zealand families (n=480) and an independent Norwegian case-control cohort (1,139 cases, 2,269 controls). ERAP2 variants rs2549782 (Australian cohort, p uncorr=0.004, p corr=0.018) and rs17408150 (Norwegian cohort, p uncorr=0.009, p corr=0.039) showed significant experiment-wide corrected associations with preeclampsia. ERAP1 variants also showed borderline associations (rs3734016, p uncorr=0.009 in Australia; rs34750, p uncorr=0.011 in Norway).