Laboratory of Human Microbiome and Longevity, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan.
NJSC Medical University Astana, Department of Internal Medicine with the Course of Gastroenterology, Endocrinology and Pulmonology, Nur-Sultan, Kazakhstan.
Dis Markers. 2022 May 11;2022:2744762. doi: 10.1155/2022/2744762. eCollection 2022.
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia.
Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. . Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin.
Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.
类风湿关节炎（RA）是一种病因不明的自身免疫性疾病，由于关节和关节外损伤导致残疾。RA 的患病率是可变的。该疾病在女性中最为常见，比例为 3：1。环境和宿主因素的相互作用导致 RA 的发展。目前，全基因组关联研究（GWAS）为揭示 RA 的遗传背景提供了机会。抗瓜氨酸肽抗体（ACPA）是一种高度特异性的 RA 抗体，与不良预后和 RA 严重程度相关，并受许多基因调控。我们的研究旨在调查哈萨克斯坦 RA 患者中是否存在与 ACPA 存在相关的临床和遗传方面。实际上，关于这个主题的可用研究集中在白人和东亚人群（主要是日本人和中国人），从中亚获得的数据很少。
我们的研究包括 70 名 RA 患者。采集患者的血液样本，通过实时聚合酶链反应（RT-PCR）对 14 个 SNP 进行基因分型。进行了一般检查、病史和临床及实验室数据收集。使用 R 统计软件进行统计分析。我们的研究表明，ACPA 阳性与 Fc 受体样 3（FCRL3）显著相关，而 ACPA 阴性与信号转导和转录激活因子 4（STAT4）基因显著相关，但与 T 细胞活化 Rho GTP 酶激活蛋白（TAGAP）无关。此外，ACPA 阳性与放射学进展、类风湿因子（RF）、红细胞沉降率（ESR）、RA 发病年龄、患者整体评估、体重指数（BMI）和γ球蛋白有关。
在我们的队列中，没有复制以前在白人和亚洲人群中发现的 11 个与 ACPA 显著相关的 SNP。需要对更大的队列进行进一步研究，以更高的置信水平和更强的统计能力来证实我们的发现。
