rs30187

This case-control study examined associations between four ERAP1 SNPs (rs26653 G/C [R127P], rs26618 T/C [I276M], rs30187 C/T [K528R], rs27044 C/G [Q730E]) and non-small cell lung cancer (NSCLC) risk in Chinese and Polish populations. All four SNPs showed significant associations with NSCLC in Chinese patients (n=420 cases, 385 controls) but not in Polish patients (n=317 cases, 506 controls), with the differences explained by substantially different SNP allele frequencies between populations.

This case-control study investigates ERAP1 and ERAP2 gene polymorphisms and their association with psoriatic arthritis (PsA) in a Romanian population of 98 PsA patients and 247 controls. The results show that ERAP2 rs2248374 is associated with increased PsA risk (p=0.02, OR 1.59) especially in HLA-B27 negative patients, while ERAP1 rs30187 is strongly associated with HLA-B27 positive PsA (p=0.005, OR 2.73). This is reported as the first study investigating ERAP2 polymorphisms in relation to PsA susceptibility.

Genetic dissection of acute anterior uveitis (AAU) using high-density Immunochip genotyping in 1,711 AAU cases and 10,000 controls identifies HLA-B27 tag SNP rs116488202 (OR=16.8, P<1×10⁻³⁰⁰) as the strongest association, and three genome-wide significant non-MHC loci (IL23R, chromosome 2p15 intergenic region, and ERAP1) shared with ankylosing spondylitis. Five additional suggestive loci including IL10-IL19, IL18R1-IL1R1, IL6R, KIF21B, and EYS are identified, with shared genetic pathways with inflammatory bowel disease suggesting common etiologic mechanisms.

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.

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 case-control study examined the association between SNP polymorphisms in ERAP1, TGFB1, and TLR9 genes and ankylosing spondylitis (AS) susceptibility in a Chinese Han population (328 AS patients, 627 controls). Strong association was found for ERAP1 rs27044 (OR=3.88, P<0.0001), with the GG genotype conferring increased risk. No significant associations were observed for TGFB1 rs1800470 or TLR9 rs55704465, indicating that ERAP1 is a major non-HLA AS-associated locus in Chinese populations.

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.

This case-control study of 735 Han Chinese ankylosing spondylitis (AS) patients and 1,204 healthy controls found no association between rs4552569 and rs17095830 polymorphisms and AS susceptibility, contradicting a prior GWAS finding. However, rs17095830 showed significant association with inflammatory bowel disease as an AS complication (P=0.0180, OR=1.739, 95% CI=1.146–2.639), and rs30187 (ERAP1) was associated with disease severity measured by BASDAI.

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).

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.