生物
类风湿性关节炎
遗传学
混合模型
肿瘤坏死因子α
人口
免疫学
计算生物学
环境卫生
医学
统计
数学
作者
Pedro Augusto Silva dos Santos Rodrigues,A. Oliveira,Kelly Nascimento Brandão,Lilian de Sá Garcia Landeiro,Laryssa Cardoso Calmon,João Victor Andrade Cruz,Mailane dos Anjos Silva,Ana Flávia Silva Rocha,Dorotéia Rossi Silva Souza,Aramís Tupiná Alcântara de Moreira,Javier Santos,Tiago Felipe de Abreu Santos,Gabriela Pimentel Pinheiro,Álvaro Augusto Souza da Cruz Filho,Camila Alexandrina Figueiredo,P Moura Santos,Ryan dos Santos Costa
出处
期刊:Gene
[Elsevier]
日期:2024-11-01
卷期号:928: 148804-148804
标识
DOI:10.1016/j.gene.2024.148804
摘要
Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease that mainly affects the joints, on reducing functional capacity and impacting quality of life. Cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are crucial in the pathogenesis and treatment of this disease. Some patients using TNF inhibitors (TNFi) do not respond or lose their response to these medications. Clinical, sociodemographic, and genetic data were used to evaluate the associations of single nucleotide polymorphisms (SNP) in TNF, TNFRSF1A, and TNFRSF1B genes with the diagnosis of RA, standardized score results, laboratory tests, and response to TNFi. In one subsample, TNF and IL-6 serum levels cytokines were performed. A total of 654 subjects (360 healthy controls and 294 diagnosed with RA) were included in the analysis. Higher levels of TNF have been found in individuals diagnosed with RA. IL-6 levels were higher in individuals who did not respond to TNFi treatment, while responders had levels comparable to those without the disease. No associations were found between the SNPs studied and the diagnosis of RA; however, rs767455-C seems to play a role in the response to golimumab treatment, being related to better therapeutic response and lower mean serum leukocyte levels. In addition, rs1061622-G was associated with poorer functional capacity and rs1800629-A was associated with higher leukocyte values and serum transaminase levels. The rs1061622-G and rs767455-C may play a role in the response to TNFi treatment, especially for patients using golimumab, although they do not seem to be associated with the diagnosis of RA. Polymosphisms in the TNF pathway may impact baseline levels of immune cells and markers of renal and hepatic function in RA patients. Our results highlight the importance of evaluating the impact of these polymorphisms on TNFi response and safety, particularly in larger-scale studies.
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