Vetchinkina Ekaterina A, Mikhaylenko Dmitry S, Kuznetsova Ekaterina B, Deryagina Tatiana A, Alekseeva Ekaterina A, Bure Irina V, Zamyatnin Andrey A, Nemtsova Marina V
Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.
Research Centre for Medical Genetics, 115522 Moscow, Russia.
J Pers Med. 2021 May 25;11(6):469. doi: 10.3390/jpm11060469.
Rheumatoid arthritis (RA) is a multifactorial disease caused by a genetic predisposition and environmental factors. Predisposing alleles of various genes have a relatively small influence on the disease risk when they appear separately, but in combination, they predispose an individual to RA development. We genotyped 125 patients with RA including 60 SNPs and sequenced coding part of six genes by next-generation sequencing (NGS) technology on a target panel (IAD177464_185). According to our data, the alleles HLA-DRB104, HLA-DRB101, HLA-B27, (rs2476601), (rs1800629), (rs2842934), and (rs2243250), and genotypes HLA-DRB104:04, HLA-DRB1*01:16, (rs2476601), (rs2842934), were significantly associated with the RA development. Associations with clinical criteria (DAS28-CRP, HAQ-DI, and CDAI) and biochemical factors were investigated. We have shown that the genotypes (rs11203367, rs2240340, rs11203366, and rs874881) are significantly associated with the baseline levels of DAS28-CRP, HAQ-DI, and CDAI; genotypes (rs7530511) and (rs748004, rs2228144) with the level of anti citrullinated peptide antibodies (ACPA); the genotypes (rs3213422) and (rs180113) with the concentration of C-reactive protein (CRP); and the genotypes (rs2104286), (rs11541076), and (rs1801275) with the level of rheumatoid factor (RF). Application of targeted NGS panel contributes to expanded genotyping to identify risk groups among the RA patients.
类风湿性关节炎（RA）是一种由遗传易感性和环境因素引起的多因素疾病。各种基因的易感等位基因单独出现时对疾病风险的影响相对较小，但组合在一起时，会使个体易患RA。我们对125例RA患者进行了基因分型，包括60个单核苷酸多态性（SNP），并通过下一代测序（NGS）技术在目标板（IAD177464_185）上对六个基因的编码部分进行了测序。根据我们的数据，等位基因HLA-DRB104、HLA-DRB101、HLA-B27、（rs2476601）、（rs1800629）、（rs2842934）和（rs2243250），以及基因型HLA-DRB104:04、HLA-DRB1*01:16、（rs2476601）、（rs2842934）与RA的发生显著相关。研究了与临床标准（DAS28-CRP、HAQ-DI和CDAI）及生化因素的关联。我们已经表明，基因型（rs11203367、rs2240340、rs11203366和rs874881）与DAS28-CRP、HAQ-DI和CDAI的基线水平显著相关；基因型（rs7530511）和（rs748004、rs2228144）与抗瓜氨酸化肽抗体（ACPA）水平相关；基因型（rs3213422）和（rs180113）与C反应蛋白（CRP）浓度相关；基因型（rs2104286）、（rs11541076）和（rs1801275）与类风湿因子（RF）水平相关。应用靶向NGS板有助于扩大基因分型，以识别RA患者中的风险群体。
