Londono John, Santos Ana M, Rueda Juan C, Calvo-Paramo Enrique, Burgos-Vargas Ruben, Vargas-Alarcon Gilberto, Martinez-Rodriguez Nancy, Arias-Correal Sofia, Muñoz Guisselle-Nathalia, Padilla Diana, Cuervo Francy, Reyes-Martinez Viviana, Bernal-Macías Santiago, Villota-Eraso Catalina, Avila-Portillo Luz M, Romero Consuelo, Medina Juan F
Department of Rheumatology, Universidad de la Sabana, Chia, Colombia
Department of Rheumatology, Hospital Militar Central, Bogota, Colombia.
RMD Open. 2020 Sep;6(2). doi: 10.1136/rmdopen-2020-001250.
To determine the association between endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 single-nucleotide polymorphisms (SNPs) and human leukocyte antigens (HLA)-B27+ or HLA-B15+ patients with spondyloarthritis (SpA).
104 patients with SpA according to Assessment of Spondyloarthritis International Society criteria were included in the study. HLA typing was performed by PCR. The polymorphisms were determined by real-time PCR on genomic DNA using customised probes for SNPs rs27044, rs17482078, rs10050860 and rs30187 in , and rs2910686, rs2248374 and rs2549782 in .
70 of the104 patients with SpA were HLA-B27+ and 34 were HLA-B15+. The distribution of ERAP1 and ERAP2 SNPs between the HLA-B15+ and HLA-B27+ patients with SpA did not reveal differences. Likewise, no differences in the frequencies of ERAP1 SNP haplotypes and alleles HLA-B15 or HLA-B27 were found. Interestingly, however, the frequencies of three particular haplotypes formed by ERAP2 SNPs rs2549782/rs2248374/rs2910686 varied between HLA-B15+ and HLA-B27+ patients: the ERAP2 SNPs haplotype TGT was more common in HLA-B15+ patients with SpA (OR 2.943, 95% CI 1.264 to 6.585; P=0.009), whereas the ERAP2 SNP haplotypes TGC and CAT were more associated with HLA-B27+ patients with SpA: (OR 4.483, 95% CI 1.524 to 13.187; p=0.003) and (OR 9.014, 95% CI 1.181 to 68.807; p=0.009), respectively.
An association was found between HLA-B15+ patients with SpA and haplotype TGT of ERAP2 SNPs. On the other hand, HLA-B27+ patients with SpA were associated with ERAP2 haplotypes TGC and CAT. These associations could be related to the clinical presentation of the disease, specifically with a peripheral or axial predominance, respectively.
确定内质网氨肽酶（ERAP）1和ERAP2单核苷酸多态性（SNP）与脊柱关节炎（SpA）的人类白细胞抗原（HLA）-B27阳性或HLA - B15阳性患者之间的关联。
根据国际脊柱关节炎评估协会标准，104例SpA患者纳入研究。通过聚合酶链反应（PCR）进行HLA分型。使用针对rs27044、rs17482078、rs10050860和rs30187的SNP定制探针以及针对rs2910686、rs2248374和rs2549782的定制探针，通过实时PCR在基因组DNA上确定多态性。
104例SpA患者中，70例为HLA - B27阳性，34例为HLA - B15阳性。SpA的HLA - B15阳性和HLA - B27阳性患者之间ERAP1和ERAP2 SNP的分布未显示差异。同样，未发现ERAP1 SNP单倍型和等位基因HLA - B15或HLA - B27频率的差异。然而，有趣的是，由ERAP2 SNPs rs2549782/rs2248374/rs2910686形成的三种特定单倍型的频率在HLA - B15阳性和HLA - B27阳性患者之间有所不同：ERAP2 SNPs单倍型TGT在SpA的HLA - B15阳性患者中更常见（比值比2.943，95%置信区间1.·264至6.585；P = 0.009），而ERAP2 SNP单倍型TGC和CAT与SpA的HLA - B27阳性患者更相关：分别为（比值比4.483，95%置信区间1.524至13.187；p = 0.003）和（比值比9.014，95%置信区间1.181至68.807；p = 0.009）。
发现SpA的HLA - B·5阳性患者与ERAP2 SNPs的单倍型TGT之间存在关联。另一方面，SpA的HLA - B27阳性患者与ERAP2单倍型TGC和CAT相关。这些关联可能与疾病的临床表现有关，分别具体与外周或轴向优势有关。
