Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study
| Autor: | Alfonso González-Utrilla, Carmen Belén Lupiañez, L. M. Canet, Antonio García, Eduardo Collantes, Juana Segura-Catena, María José Soto-Pino, João Eurico Fonseca, Lurdes Romani, Miguel Ángel López Nevot, Alejandro Escudero, Eva Perez-Pampin, Helena Canhão, Juan Sainz, I. Filipescu, Miguel Ferrer, Rafael Cáliz |
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| Rok vydání: | 2015 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Population Single-nucleotide polymorphism Polymorphism Single Nucleotide Arthritis Rheumatoid Internal medicine Genotype Genetics medicine SNP Humans Receptors Tumor Necrosis Factor Type II Genetic Predisposition to Disease General Pharmacology Toxicology and Pharmaceutics Allele education Molecular Biology Genetics (clinical) Genetic Association Studies Aged education.field_of_study business.industry Tumor Necrosis Factor-alpha Middle Aged medicine.disease Rheumatoid arthritis Antirheumatic Agents Case-Control Studies Molecular Medicine Population study Female Tumor necrosis factor receptor 2 business |
| Zdroj: | Pharmacogenetics and genomics. 25(7) |
| ISSN: | 1744-6880 |
| Popis: | BACKGROUND Recent research suggests that genetic variants in the tumor necrosis factor receptor 2 (TNFRSF1B) gene may have an impact on susceptibility to rheumatoid arthritis (RA) and drug response. The present population-based case-control study was carried out to evaluate whether 5 tagging single-nucleotide polymorphisms (SNPs) within the TNFRSF1B gene are associated with the risk of RA and response to antitumor necrosis factor (TNF) drugs. METHODS The study population included 1412 RA patients and 1225 healthy controls. A subset of 596 anti-TNF-naive RA patients was selected to assess the association of TNFRSF1B SNPs and drug response according to the EULAR response criteria. RESULTS We found that carriers of the TNFRSF1Brs3397C allele had a significantly increased risk of developing RA (P=0.0006). Importantly, this association remained significant after correction for multiple testing. We also confirmed the lack of association of the TNFRSF1Brs1061622 SNP with the risk of RA in the single-SNP analysis (P=0.89), but also through well-powered meta-analyses (PDOM=0.67 and PREC=0.37, respectively). In addition, our study showed that carriers of the TNFRSF1Brs3397C/C, TNFRSF1Brs1061622G/G, and TNFRSF1Brs1061631A/A genotypes had an increased risk of having a worse response to anti-TNF drugs at the level of P less than 0.05 (P=0.014, 0.0085 and 0.028, respectively). We also observed that, according to a log-additive model, carriers of the TNFRSF1Brs3397C or TNFRSF1Brs1061622G alleles showed an increased risk of having worse response to anti-TNF medications (P=0.018 and 0.0059). However, the association of the TNFRSF1Brs1061622 SNP only reached marginal significance after correction for multiple testing according to a log-additive model (P=0.0059) and it was not confirmed through a meta-analysis (PDOM=0.12). CONCLUSION Our results suggest that the TNFRSF1Brs3397 variant may play a role in modulating the risk of RA, but does not provide strong evidence of an impact of TNFRSF1B variants in determining response to anti-TNF drugs. |
| Databáze: | OpenAIRE |
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