Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis
Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis
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DOI：
10.1136/ard.2004.034173
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发表时间：
2005-09-01
影响因子：
27.4
通讯作者：
Silman, A
中科院分区：
文献类型：
--
作者：
Barton, A;Bowes, J;Silman, A
背景资料：肽基精氨酸脱亚胺酶4（PADI 4）基因的功能单倍型最近已被确定为类风湿性关节炎易感基因在日本，但不是在英国人口。这种差异的一个可能的解释是，该基因决定了炎症性多关节炎（IP）的严重程度，而不是易感性，并且英国和日本队列在结局方面存在差异。目的：研究个体PADI 4单核苷酸多态性（SNP）和单倍型之间的关联，以及IP患者5年内糜烂的发展和严重程度。方法：来自NOAR初始IP患者队列的438例患者在出现早期IP后5年接受X线检查。研究了与四个外显子SNP（padi4_89*G/A、padi4_90*T/C、padi4_92*G/C和padi4_104*T/C）的关联，这些SNP定位于PADI 4基因并定义了先前报道的与类风湿性关节炎相关的单倍型。患者进行了比较的存在，程度和进展的糜烂的5年和存在的瓜氨酸肽抗体（抗CCP抗体）。结果：有没有个别PADI 4单核苷酸多态性或单倍型和发展之间的关联或糜烂的程度由5年。将分析限制在5年内满足ACR类风湿关节炎标准的患者并没有改变结论。无关联存在的抗CCP抗体detected.Conclusions：没有证据表明，PADI 4基因与严重程度评估的糜烂性结局在5年或存在抗CCP抗体的IP患者。
Background: A functional haplotype of the peptidylarginine deiminase 4 (PADI4) gene has recently been identified as a rheumatoid arthritis susceptibility gene in a Japanese but not in a UK population. One possible explanation for this disparity is that the gene determines severity of rather than susceptibility to inflammatory polyarthritis (IP) and that the UK and Japanese cohorts differed in terms of outcome.Aim: To examine the association between individual PADI4 single nucleotide polymorphisms ( SNPs) and haplotypes, with the development and severity of erosions by five years in patients with IP.Methods: 438 patients from the NOAR inception cohort of patients with IP were x rayed five years after presentation with early IP. Association with four exonic SNPs ( padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with rheumatoid arthritis, was investigated. Patients were compared for the presence, extent, and progression of erosions by five years and the presence of antibodies to citrullinated peptide (anti-CCP antibodies).Results: There was no association between individual PADI4 SNPs or haplotypes and the development or extent of erosions by five years. Restricting analysis to patients who satisfied ACR criteria for rheumatoid arthritis by five years did not alter the conclusions. No association with presence of anti-CCP antibodies was detected.Conclusions: No evidence was found for association of the PADI4 gene with severity as assessed by erosive outcome at five years or with presence of anti-CCP antibodies in patients with IP.