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Association of biomarkers of inflammation and HLA-DRB1 gene locus with risk of developing rheumatoid arthritis in females.
Rheumatology International ( IF 4 ) Pub Date : 2019-08-26 , DOI: 10.1007/s00296-019-04429-y
Biljana Klimenta 1 , Hilada Nefic 2 , Nenad Prodanovic 3 , Radivoj Jadric 4 , Fatima Hukic 5
Affiliation  

Rheumatoid arthritis (RA) is an autoimmune disease causing chronic inflammation of the joints. Multiple factors, including HLA-DRB1 gene variants, influence the susceptibility to RA. The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. In this study, we compared the inflammatory biomarkers values, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), between patients with RA and healthy control group of females of the Public Institution Health Centre of Sarajevo Canton. In addition, we estimated the frequencies of the HLA-DRB1 gene variants and their association with the risk for RA development in females. The haematological and biochemical tests were completed on automated analyzers. To assess the association between the HLA-DRB genes and the risk of RA in females, low-resolution genotyping of the HLA-DRB1, DRB3, DRB4, and DRB5 gene loci was performed by the sequence-specific polymerase chain reaction method (PCR-SSP). ESR and CRP were the most sensitive acute-phase reactants in females with RA and there was a correlation between ESR and CRP values in RA patients. There was significantly positive association between of the HLA-DRB1*03, *04, *08, *10, *11, and *14 variants and elevated values of ESR in RA patients, but negative between HLA-DRB1*03, *13 and *15 alleles and elevated CRP values. Furthermore, our results confirm genetic susceptibility to RA in a female population to the members of the HLA-DRB1*04 and *03 allelic groups, the DRB1*04/DRB1*04 and DRB1*03/DRB1*04 genotypes, and the DRB1*04-DRB4* or DRB1*03-DRB3* haplotypes, which, therefore, represent risk factors for the development of this disease. According to our results, the DRB1*01/DRB1*15 and DRB1*07/DRB1*16 genotypes and the HLA-DRB5 gene locus represent a protective factor for RA. The presence of specific HLA-DRB1 gene variants increases the risk of developing RA, while other variants provide protection against disease. Therefore, HLA typing could be helpful in the prediction of RA development and establishing and confirming a definitive diagnosis of autoimmune diseases in some subjects. A strong association with the higher levels of ESR and CRP could be used to establish definitive diagnosis and introduce of early treatment of RA to prevent the occurrence of RA symptoms.

中文翻译:

炎症和HLA-DRB1基因位点的生物标志物与女性发生类风湿关节炎的风险相关。

类风湿关节炎(RA)是一种自身免疫性疾病,会引起关节的慢性炎症。包括HLA-DRB1基因变异在内的多种因素都会影响RA的易感性。HLA-DRB1基因是称为人类白细胞抗原(HLA)复合体的基因家族的一部分。在这项研究中,我们比较了RA患者与萨拉热窝州公共机构健康中心女性健康对照组之间的炎症生物标记物值,包括红细胞沉降率(ESR)和C反应蛋白(CRP)。此外,我们估计了HLA-DRB1基因变体的频率及其与女性RA发育风险的关系。血液和生化测试在自动分析仪上完成。为了评估HLA-DRB基因与女性RA风险之间的关联,HLA-DRB1,DRB3,DRB4和DRB5基因位点的低分辨率基因分型通过序列特异性聚合酶链反应法(PCR-SSP)进行。ERA和CRP是女性RA患者中最敏感的急性期反应物,RA患者的ESR和CRP值之间存在相关性。RA患者的HLA-DRB1 * 03,* 04,* 08,* 10,* 11和* 14变异与ESR值之间呈显着正相关,而HLA-DRB1 * 03,* 13之间呈负相关* 15个等位基因和较高的CRP值。此外,我们的结果证实了女性人群中RA对HLA-DRB1 * 04和* 03等位基因组,DRB1 * 04 / DRB1 * 04和DRB1 * 03 / DRB1 * 04基因型以及DRB1的遗传易感性* 04-DRB4 *或DRB1 * 03-DRB3 *单倍型,因此代表该疾病发展的危险因素。根据我们的结果,DRB1 * 01 / DRB1 * 15和DRB1 * 07 / DRB1 * 16基因型和HLA-DRB5基因位点代表RA的保护因子。特定的HLA-DRB1基因变体的存在增加了患RA的风险,而其他变体则提供了抗疾病的保护。因此,HLA分型可能有助于预测RA的发展以及在某些受试者中建立和确认对自身免疫性疾病的明确诊断。与较高的ESR和CRP水平密切相关可以用于确定性诊断,并引入RA的早期治疗以预防RA症状的发生。特定的HLA-DRB1基因变体的存在增加了RA患病的风险,而其他变体则提供了抗疾病的保护。因此,HLA分型可能有助于预测RA的发展以及在某些受试者中建立和确认对自身免疫性疾病的明确诊断。与较高的ESR和CRP水平密切相关可以用于确定性诊断,并引入RA的早期治疗以预防RA症状的发生。特定的HLA-DRB1基因变体的存在增加了患RA的风险,而其他变体则提供了抗疾病的保护。因此,HLA分型可能有助于预测RA的发展以及在某些受试者中建立和确认对自身免疫性疾病的明确诊断。与较高的ESR和CRP水平密切相关可以用于确定性诊断,并引入RA的早期治疗以预防RA症状的发生。
更新日期:2019-08-26
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