Tumor Necrosis Factor Alpha -308G/A Gene Polymorphisms Combined with Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio Predicts the Efficacy and Safety of Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis Arthritis

Abstract

Background: TNF-α has been reported to be closely associated with autoimmune inflammatory diseases. This study aims to investigate the role of TNF-α -308(rs1800629) G/A gene polymorphisms as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of TNF inhibitors (TNFi) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriasis arthritis (PsA).Methods: A total of 515 subjects (181 AS, 144 RA, 48 PsA, 10 hyperbilirubinemia, 10 hyperlipidemia and 122 healthy control) were recruited in this study. The accuracy of RT-PCR methods for identifying individual TNF-α -308 genotypes was assessed using sequencing as the gold standard. Baseline NLR and PLR of patients with AS, RA and PsA and healthy controls (HC) were calculated and compared. Meanwhile, differences between responders and non-responders to TNFi treatment as well as between individuals with and without adverse effects (AE) among responders were compared.Results: The RT-PCR method is stable and reliable for TNF-α -308G/A gene polymorphism analysis, independent of sample status. The GG genotype was overwhelmingly represented, with relatively few GA genotype, whilst the AA genotype was not detected in this study. There was no observed association between TNF-α-308G/A polymorphism and susceptibility in AS, RA or PsA patients. Patients with AS, RA, and PsA had a higher NLR, compared to the HC group. Apart from PsA patients, AS and RA patients had a higher PLR, compared to the HC group. NLR was positively correlated with PLR. Furthermore, a lack of response was more frequently observed in AS and RA patients that carrying the GA genotype than the GG genotype. AS and RA patients with AE had higher NLR and PLR, compared with the non-AE group.Conclusion: Our study preliminarily shown that combining TNF-α -308G/A polymorphisms with NLR and PLR can predict the responsiveness and safety of anti-TNF therapy in patients with AS or RA.

The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough

“…Nevertheless, the field of allergic diseases had few Frontiers in Genetics frontiersin.org corresponding reports. TaqMan-MGB qPCR offered a reliable and affordable method for investigating SNPs with allergy disorders (Wang et al, 2021;Jin et al, 2022;Wang et al, 2022). Using this technology, we initially discovered that patients with allergic cough had a different distribution of the PAI-1 rs1799762 gene than healthy people.…”

“…According to the Applied Biosystems methodology, genotyping was accomplished by TaqMan chemistry utilizing the real-time Prism 3730XL Sequence Detection System (ABI Inc. CA, United States). In our prior research, we have demonstrated the effectiveness of the TaqMan-MGB qPCR kit for the detection of gene polymorphisms (Wang et al, 2021;Jin et al, 2022;Wang et al, 2022). The Kappa test was used to examine the agreement between DNA sequencing and TaqMan-MGB qPCR, with a Kappa value of 1 and a p-value <.001.…”

Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism

“…Recurrence of VTE was defined as: [1] dissemination of thrombus to new veins or venous segments; [2] formation of new thrombus at a different site; [3] new PE [23]. Hyperbilirubinemia (HB) and hyperlipidemia (HLP) were diagnosed by combining clinical symptoms and laboratory results as described in the previous publication [8]. In addition to this, apparently healthy individuals with no family history of coagulation disorders, no malignancies, rheumatic or chronic diseases and no abnormal laboratory test results were selected as healthy controls (HC).…”

“…Given the crucial role of genetic factors in disease pathogenesis, single nucleotide polymorphisms (SNPs) have become a hot topic of research at present. In previous study, we reported the potential value of combining tumor necrosis factor-α (TNF-α) -308G/A gene polymorphism with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of anti-TNF-α therapy [8]. Some inherited polymorphisms have been identified as high-risk factors for VTE, such as 4G or 5G polymorphism of plasminogen activator inhibitor 1 (PAI-1), G1691A mutation in the F5 gene (Factor V Leiden (FVL)), G20210A of the F2 (prothrombin) gene, and C677T of the methylenetetrahydrofolate reductase (MTHFR) gene.…”

Plasminogen Activator Inhibitor-1 4G/5G (rs1799889) Polymorphism in Chinese Patients with Diabetes Mellitus and Hypertension

“… 8 In addition to this, SNPs have also been shown to be closely related to drug responsiveness and the safety of therapy. 9 On this basis, it would be beneficial to analyze the variations in genetic susceptibility and clinical features of individuals carrying different genotypes to better understand the role of SNPs in the pathogenesis of disease.…”