Abstract
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-DRB1*04, HLA-DRB1*01, HLA-B*27, PTPN22 (rs2476601), TNF (rs1800629), TPMT (rs2842934), and IL4 (rs2243250), and genotypes HLA-DRB1*04:04, HLA-DRB1*01:16, PTPN22 (rs2476601), TPMT (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 PADI4 genotypes (rs11203367, rs2240340, rs11203366, and rs874881) are significantly associated with the baseline levels of DAS28-CRP, HAQ-DI, and CDAI; genotypes IL23R (rs7530511) and TNFRSF1A (rs748004, rs2228144) with the level of anti citrullinated peptide antibodies (ACPA); the genotypes DHODH (rs3213422) and MTHFR (rs180113) with the concentration of C-reactive protein (CRP); and the genotypes IL2RA (rs2104286), IRAK3 (rs11541076), and IL4R (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.
Highlights
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with joint damage
The highest risk of RA among alleles of the human leukocyte antigens (HLA)-DRB1 was associated with the allele
We found that the FCGR2A [rs1801274] allele T increases the risk of RA in 1.4 times [confidence interval (CI): 1.08–1.8], p = 0.011, and the protective allele G reduces the risk of RA: odds ratio (OR) = 0.72 [CI: 0.56–0.93], p = 0.011
Summary
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with joint damage. RA is characterized by significant clinical polymorphism, progressive severe course, and serious complications, if not treated properly. Clinical and genealogical methods revealed a genetic predisposition to RA, so the disease is considered as multifactorial, arising from the interaction of unfavorable alleles of various genes and negative environmental factors [3]. The combination of several alleles associated with RA together either can result in a more severe course of the disease or become a protective factor. A contribution of molecular genetic factors to the development of RA is estimated as 50–60% [4]. Due to the high significance of hereditary factors, it remains relevant to create panels of genetic markers that reflect the risk of occurrence and characteristics of RA pathogenesis
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