PADI2 is significantly associated with rheumatoid arthritis.
PADI2 is significantly associated with rheumatoid arthritis.
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DOI：
10.1371/journal.pone.0081259
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yan X
中科院分区：
文献类型：
--
作者：
Chang X;Xia Y;Pan J;Meng Q;Zhao Y;Yan X
瓜氨酸化是肽基精氨酸转化为瓜氨酸的一种翻译后修饰，在类风湿关节炎(RA)中起着重要作用。瓜氨酸化是由一组包括PADI1、PADI2、PADI3、PADI4和PADI6在内的多肽精氨酸脱亚胺酶(PADS)催化的。许多研究表明，PADI4基因是RA的易感性因素。一些研究检测到PADI2在RA滑膜组织中的表达，提示PADI2在RA疾病中也起着重要作用。这项研究评估了PADI2编码基因与类风湿关节炎之间的可能联系。使用定制设计的Illumina 96-SNP Veracode微阵列对PAD基因座上的17个标签SNP进行了基因分型。采集RA(n = 2 6 7例)、强直性脊柱炎(AS，n = 5 1例)和健康对照组(n = 16 0例)外周血标本。用Sequenom Massarray对307名RA患者、324名AS患者和509名健康对照的基因分型结果进行了验证。免疫印迹法检测RA(n = 7)、骨性关节炎(OA，n = 7)和AS(n = 5)患者滑膜组织中PADI2的表达水平。微阵列分析显示，三个选定的PADI2 SNP(rs2235926、rs2057094、rs2076616)与RA的存在显著相关。序列分析进一步证实rs2235926(OR = 1.706733，95%CI = [1.576366-1.866587]，p = 0.000839)和rs2057094(OR = 1.360432，95%CI = [1.065483-1.869482]，p = 0.003291)对RA的易感性增加。PADI2基因座上无标签SNPs与AS显著相关。RA滑膜组织中PADI2的表达高于OA和AS患者的滑膜组织。PADI2与RA密切相关，可能参与了RA的发病机制。
Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n = 267), ankylosing spondylitis (AS, n = 51) and healthy controls (n = 160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n = 7), osteoarthritis (OA, n = 7) and AS (n = 5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR = 1.706733, 95% CI = [1.576366–1.866587], p = 0.000839) and rs2057094 (OR = 1.360432, 95% CI = [1.065483–1.869482], p = 0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease.
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作者：
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