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首页> 外文期刊>Arthritis research & therapy. >Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population
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Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population

机译：抗瓜氨酸肽/蛋白质抗体（ACPA） - Negative RA与ACPA阳性RA分享大部分易感性锁骨：日本人群中基因组关联研究的META分析

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Introduction: Although susceptibility genes for anti-citrullinated peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been successfully discovered by genome-wide association studies (GWAS), little is known about the genetic background of ACPA-negative RA. We intended to elucidate genetic background of ACPA-negative RA. Method: We performed a meta-analysis of GWAS comprising 670 ACPA-negative RA and 16,891 controls for 1,948,138 markers, followed by a replication study of the top 35 single nucleotide polymorphisms (SNPs) using 916 cases and 3,764 controls. Inverse-variance method was applied to assess overall effects. To assess overlap of susceptibility loci between ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility markers to RA in Japanese were compared between the two subsets. In addition, SNPs were stratified by the p-values in GWAS meta-analysis for either ACPA-positive RA or ACPA-negative RA to address the question whether weakly-associated genes were also shared. The correlations between ACPA-positive RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive and RF-negative subsets) were also addressed. Results: Rs6904716 in LEMD2 of the human leukocyte antigen (HLA) locus showed a borderline association with ACPA-negative RA (overall p?=?5.7?×?10?8), followed by rs6986423 in CSMD1 (p?=?2.4?×?10?6) and rs17727339 in FCRL3 (p?=?1.4?×?10?5). ACPA-negative RA showed significant correlations of ORs with ACPA-positive RA for the 21 susceptibility SNPs and non-HLA SNPs with p-values far from significance. These significant correlations with ACPA-positive RA were true for ACPA-negative RF-positive and ACPA-negative RF-negative RA. On the contrary, positive correlations were not observed between the ACPA-negative two subpopulations. Conclusion: Many of the susceptibility loci were shared between ACPA-positive and -negative RA.
机译：介绍：尽管抗瓜育肽/蛋白抗体（ACPA） - 阳性类风湿性关节炎（RA）的易感基因已被基因组 - 范围的协会研究（GWAs）成功地发现，关于ACPA阴性RA的遗传背景知之甚少。我们打算阐明ACPA阴性RA的遗传背景。方法：我们对1,948,138个标记的Gwas进行了Gwas的Meta分析，然后使用916例和3,764个对照的前35例单核苷酸多态性（SNP）的复制研究。应用逆差异法评估整体效果。为了评估ACPA阳性和阴性RA之间的敏感性基因座的重叠，在两个子集之间比较了日语中的21种易感标记的差距（或s）。此外，SNP通过GWAS阳性RA或ACPA阴性RA的GWAS META分析中的p值分层，以解决弱相关基因的问题。 ACPA阳性RA与ACPA阴性RA（类空腔因子（RF） - 阳性和RF阴性子集）之间的相关性也得到了解决。结果：人白细胞抗原的LEMD2 rs6904716（HLA）基因座，均与ACPA阴性RA（总体P？= 5.7？×10？8）显示出边界联合关联，其次是CSMD1中的RS6986423（P？=？2.4？ ×10？6）和FCRL3中的RS17727339（p？=？1.4？×10？5）。 ACPA阴性Ra显示出与21个易感性SNP和非HLA SNP的ACPA阳性RA的显着相关性，其具有远离意义的p值。对于ACPA阴性RF阳性和ACPA阴性RF阴性RA，与ACPA阳性RA的这些显着相关性是如此。相反，在ACPA阴性两种亚型之间未观察到阳性相关性。结论：在ACPA阳性和阴部RA之间共享许多易感位点。

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