A Functional Haplotype of PADI4 Gene in Rheumatoid Arthritis: Positive Correlation in a French Population
A Functional Haplotype of PADI4 Gene in Rheumatoid Arthritis: Positive Correlation in a French Population
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DOI：
10.3899/jrheum.080398
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发表时间：
2009-05-01
影响因子：
3.9
通讯作者：
Solau-Gervais, Elisabeth
中科院分区：
文献类型：
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作者：
Gandjbakhch, Frederique;Fajardy, Isabelle;Solau-Gervais, Elisabeth
客观的。肽基精氨酸脱亚胺酶 4 (PADI4) 的功能性单倍型与亚洲人群中类风湿性关节炎 (RA) 的易感性相关，但在欧洲人群中的结果却相互矛盾。我们研究了 (1) 位于 PADI4 外显子 2 的 2 个单核苷酸多态性 (SNP) 与另一个白种人群体中 RA 的关联； (2)PADI4和抗瓜氨酸蛋白(抗CCP)抗体之间的关联。方法。 DNA 样本取自 405 名法国 RA 患者和 275 名对照者。所有 RA 患者均符合美国风湿病学会修订后的标准。使用直接测序证实的PCR-RFLP方法对PADI4 89 163(G -> A)和PADI4_90 245(T -> C) SNP进行基因分型。所有患者和对照均进行了 HLA-DRB1 基因分型。使用 ELISA 技术在 243 名 RA 患者中测试了抗 CCP 抗体的存在。结果。我们重点关注 PADI4_89 163(G -> A) 和 PADI4_90 245(T -> C) SNP，它们区分了 2 个主要单倍型：AC 单倍型 (PADI4_89*A PADI4_90*C) 和 GT 单倍型 (PAD_4-89*G PADI4_90*T)，分别描述为“不敏感”和“易受影响。”在杂合状态 (p = 0.002) 和纯合状态 (RA 患者 22%，对照 13% p = 0.005) 中发现 RA 与 GT 单倍型存在之间呈正相关。观察到抗 CCP 抗体的存在但不与 GT 杂合子 (p = 0.03) 和纯合子 (p = 0.05) 单倍型之间存在相关性。未发现 HLA-DRB1 共享表位与任何 PADI4 单倍型之间存在相关性。结论。我们的研究结果证实了日本、韩国和加拿大的研究结果，并表明 PADI4 可能是白种人人群中 RA 的一种独立于 HLA-DRB1 的新易感基因。 （首次发布，2009 年 4 月 1 日；J Rheumatol 2009；36:881-6；doi: 10.3899/jrheum.080398）
Objective. A functional haplotype of peptidyl arginine deiminase 4 (PADI4) was associated with susceptibility to rheumatoid arthritis (RA) in Asian Populations, but the results are contradictory in Europeans. We investigated (1) the association of 2 single-nucleotide polymorphisms (SNP) located in exon 2 of PADI4 with RA in another Caucasian Population; and (2) the association between PADI4 and anti-citrullinated protein (anti-CCP) antibodies.Methods. DNA samples were obtained from 405 French RA patients and 275 controls. All RA patients met the revised criteria of the American College of Rheumatology. PADI4 89 163(G -> A) and PADI4_90 245(T -> C) SNP were genotyped using a PCR-RFLP method confirmed by direct sequencing. All patients and controls were genotyped for HLA-DRB1. The presence of anti-CCP antibodies was tested in 243 RA patients using in ELISA technique.Results. We focused on PADI4_89 163(G -> A) and PADI4_90 245(T -> C) SNP that distinguished 2 main haplotypes: AC haplotype (PADI4_89*A PADI4_90*C) and GT haplotype (PAD_4-89*G PADI4_90*T), described, respectively, as "nonsusceptible" and "susceptible." A positive association between RA and presence of the GT haplotype was found in the heterozygous state (p = 0.002) and the homozygous state (RA patients 22%, controls 13% p = 0.005). A correlation was observed between the presence but not the level of anti-CCP antibodies and the GT heterozygous (p = 0.03) and homozygous (p = 0.05) haplotypes. No correlation was found between the HLA-DRB1 shared epitope and any of the PADI4 haplotypes.Conclusion. Our findings confirm those of Japanese, Korean, and Canadian studies and Suggest that PADI4 may be a new susceptibility gene independent of HLA-DRB1 for RA in Caucasian populations. (First Release April 1 2009; J Rheumatol 2009;36:881-6; doi: 10.3899/jrheum.080398)