南印度泰米尔类风湿性关节炎患者瓜氨酸化标志物及PADI4等位基因易感性的病因学影响

IF 0.9 Q4 IMMUNOLOGY
V. Malini, N. Shettu, S. Murugesan
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引用次数: 0

摘要

类风湿性关节炎(RA)是一种多因素疾病,可由基因-环境相互作用引发。许多危险因素已经在不同的种族中得到承认,但它们的普遍性是模糊的。因此,我们提出确定病因对瓜氨酸化的影响,以及两者如何与肽基精氨酸脱亚胺酶4 (PADI4)多态性相互作用,在南印度泰米尔RA病例中发病。对207例RA患者和186名健康对照者进行c反应蛋白(CRP)、红细胞沉降率(ESR)、类风湿因子(RF)、抗环瓜氨酸肽(CCP)、抗sa(瓜氨酸蛋白)、抗瓜氨酸α-烯醇化酶肽-1 (CEP-1)和疾病活动性评分-28 (DAS-28)的检测。通过问卷调查获得的既往暴露情况所研究的病因危险因素。RA家族史、手术/损伤史和基孔肯雅病毒(CHIKV)感染对RA的发生有显著影响(p < 0.05),尤其是基孔肯雅病毒(CHIKV)感染(OR = 6.66, 95% CI 3.92 ~ 11.32, p = 0.001)。引人注目的是,67.1%的手术/损伤患者和80%的暴露于CHIKV的患者在一年内发病。RA合并蛀牙对RF、抗ccp、抗sa频率及抗cep -1水平均有影响(p < 0.05)。由于感染病例具有显著的抗sa水平(p = 0.04)和频率(p = 0.01),通过Sanger测序对感染病例进行PADI4_92 (rs874881)、104 (rs1748033)和94 (rs2240340)基因多态性分型,提示PADI4具有发生CHIKV诱导RA的风险(p < 0.05)。这是关于CHIKV可能通过静脉蛋白瓜氨酸化促进类风湿关节炎发展的初步报告。FHRA、手术/损伤、CHIKV和吸烟是主要的类风湿性关节炎风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of etiological factors on citrullination markers and susceptibility of PADI4 allele for CHIKV induced rheumatoid arthritis among South Indian Tamil RA cases
Rheumatoid arthritis (RA) is a multifactorial disease which can be triggered by gene-environment interactions. Numerous risk factors have been acknowledged in varied ethnicities, but their generalizability is vague. Hence, proposed to identify impact of etiology on citrullination and how both interact with peptidyl arginine deiminase 4 (PADI4) polymorphism in RA onset among South Indian Tamil RA cases. Studied 207 RA cases and 186 healthy controls for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), anti-Sa (citrullinated vimentin), anti-citrullinated α-enolase peptide-1 (CEP-1) and diseases activity score-28 (DAS-28). Past exposure to studied etiological risk factors obtained through questionnaire. Family history of RA (FHRA), surgery/injury and chikungunya virus (CHIKV) infection significantly contributed to RA (p < 0.05) particularly CHIKV (OR = 6.66, 95% CI 3.92–11.32, p = 0.001). Strikingly, 67.1% of surgery/injury and 80% of CHIKV exposed patients had RA onset within a year. RA cases with tooth decay had impact on RF, anti-CCP, anti-Sa freequeny and anti-CEP-1 level (p < 0.05).Since CHIKV infected cases showed significant anti-Sa (p = 0.04) level and frequency (p = 0.01), they were genotyped for polymorphism in PADI4_92 (rs874881), 104 (rs1748033) and 94 (rs2240340) by Sanger's sequencing which demonstrated that PADI4 confers risk (p < 0.05) for the onset of CHIKV induced RA. This is the initial report that CHIKV may contribute to RA development via vimentin citrullination. FHRA, surgery/injury, CHIKV and smoking posed a key RA risk.
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