Usefulness of Cytokine Gene Polymorphisms for the Therapeutic Choice in Japanese Patients with Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis (RA) is characterized by systemic synovitis with bone erosion and joint cartilage degradation. Although the analysis of polymorphisms in cytokineencoding genes is important or understanding the pathophysiology of RA and selecting appropriate treatment for it, few studies have examined such single-nucleotide polymorphisms (SNPs) specifically in Japanese patients. This study was established to investigate the associations between polymorphisms in cytokine-encoding genes, autoantibodies and therapeutic responses in Japanese RA patients. Methods: The subjects in this study consisted of 100 RA patients and 50 healthy controls. We extracted data on sex, age, disease duration, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and therapeutic responses, including to methotrexate (MTX) and biological disease-modifying antirheumatic drugs (DMARDs). Genomic DNA was isolated from peripheral blood, which was genotyped for IL-10, TNF-α, TGF-β 1 , and IFN-γ polymorphisms. Results: Regarding IL-10 (−592 C/A and −819 C/T), significant decreases in the frequencies of the IL-10 (−592) CC genotype and (−819) CC genotype were found in RA patients compared with the levels in controls. For IFN-γ (+874 T/A), a significant decrease in the frequency of the TT genotype was found in RA patients compared with that in controls. Regarding TGF-β 1 (+869 T/C), patients with positivity for anti-CCP antibody had a significantly lower frequency of the CC genotype than those with negativity for it. Furthermore, the IL-10 (−592) CC genotype and (−819) CC genotype might be related to the biological DMARD-response. Conclusion:Our results suggest that the analysis of polymorphisms in cytokine-encoding genes may be useful when selecting treatment for Japanese RA patients.

Association between the interferon‐γ +874 T/A polymorphism and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: A meta‐analysis

“…The distribution of genotypes in the normal control groups was not consistent with HWE in two studies (Harsini et al, 2016;Tsujimoto et al, 2021). 9,16 However, exclusion of these studies did not markedly affect the results of our meta-analysis of the association between the IFN-γ +874 T/A polymorphism and SLE or RA (Tables 3 and 4).…”

“…Seven hundred forty‐nine reports were identified by electronic search, and a total of nine studies, with six studies on SLE and three studies on RA, were included in the meta‐analysis. These studies contained 1839 patients and 2272 controls (Table 1, Figure 1) (Al‐Kholy et al., 2016; Angelo et al., 2015; da Silva et al., 2014; Harsini et al., 2016; Kim et al., 2010; Liu et al., 2021; Mahmoud et al., 2016; Tangwattanachuleeporn et al., 2007; Tsujimoto et al., 2021). Disease‐specific meta‐analysis was performed, and ethnicity‐specific meta‐analysis was conducted using data for the Asian, Arab and South American populations.…”

“…Several studies have shown that the IFN‐γ +874 T/A polymorphism is associated with SLE and RA, whereas other studies have found no connections (Al‐Kholy et al., 2016; Angelo et al., 2015; da Silva et al., 2014; Harsini et al., 2016; Kim et al., 2010; Liu et al., 2021; Mahmoud et al., 2016; Tangwattanachuleeporn et al., 2007; Tsujimoto et al., 2021). Small sample numbers, limited statistical power, ethnic differences and clinical heterogeneity are most likely responsible for these discrepancies.…”

Effect of Cytokine Gene Polymorphisms on Eltrombopag Reactivity in Japanese Patients with Immune Thrombocytopenia

“…The details have already been reported. 42 Polymorphisms in the TNF-α, TGF-β 1 , IL-10, and IFN-γ genes were analyzed using a PCR-SSP method using the Cytokine Genotyping Tray (One Lambda Inc., Los Angeles, CA, USA). For the cytokines under investigation, the following polymorphisms were analyzed.…”

Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis

“…12,[36][37][38][39][40] Interestingly, most of the reports investigated on association between IFN-γ +874 T>A polymorphism and RA could not establish a significant relationship. 7,[41][42][43] Meta-analysis is a powerful tool to combine similar investigations, increase the power of the study, and draw a definitive conclusion. We conducted a meta-analysis of earlier published literature to reveal the association of IFN-γ +874 T>A with susceptibility to development of RA and SLE.…”