Among the 16 AS-associated variants, rs30187 showed weaker risk effect while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than Caucasians.
Segregating according to HLAB27 status did not alter the lack of association. rs30187 SNP in ERAP1 does not confer risk of developing ERA or AS in the Asian Indian population.
The risk of AS is increased in patients possessing endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphisms rs30187 and rs27044 encoding amino acid changes K528R and Q730E, respectively.
The ERAP1 rs27044/rs30187 haplotype C/T is associated with lower risk of extraspinal disease and systemic inflammation in Nordic AS patients but has no impact on IL-6 or TNF levels.
The meta-analysis revealed a significant association between AS and the minor alleles of the rs30187 polymorphism in all study subjects (OR = 1.255, 95 % CI = 1.147-1.373, P = 8.0 × 10(-8)).
The significant alterations in the B*27:05 peptidome and the structural features of the peptides that determine their differential expression in distinct ERAP1 contexts account for the association of the R528K polymorphism with AS.
The rs17482078/rs10050860/rs30187-CCT haplotype was significantly associated with increased risk of SpA in both cohorts (P(combined)= 9.08×10(-4)), including AS and non-AS (P(combined)=6.16×10(-4) and P(combined)=0.049, respectively), whereas the -TTC haplotype was associated with reduced risk of SpA, including AS and non-AS (P(combined)=2.36×10(-7), P(combined)= 5.69×10(-6) and P(combined)= 2.13×10(-4), respectively).
For the general group of AS, the carriers of minor alleles showed an increased risk for the disease (OR 1.92, 95% CI 1.17-3.13 for rs30187, OR 1.74, 95% CI 1.08-2.80 for rs27044).
Except in rs27434 (P = 0.23), the significant correlation between ERAP1 polymorphisms and AS susceptibility has been detected in 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).
Two specific haplotypes including: rs30187/ rs469876/ rs13167972/ rs27434 TAAA and CAGG were associated with increased and decreased risk of AS in Iranian population, respectively.
This meta-analysis shows that the rs27044, rs17482078, rs10050860, rs30187, and rs2287987 polymorphisms of ERAP1 are associated with the development of AS in Europeans.
199 multiplex families with AS with four non-synonymous single nucleotide polymorphisms (SNPs), three in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene (rs27044, rs10050860 and rs30187) and one in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene (rs2549782), were genotyped and family-based association analyses were performed.
A specific ERAP1 haplotype, rs27044/10050860/30187-CCT, was strongly associated with increased risk of AS in all 3 case-control cohorts (pooled odds ratio [OR] 1.81, 95% confidence interval [95% CI] 1.46-2.24; P=7x10(-8)), while a second specific ERAP1 haplotype, rs30187/26618/26653-CTG, reduced the disease risk (pooled OR 0.77, 95% CI 0.67-0.88; P=9x10(-5)).