Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Canet, Luz M.; Filipescu, Ileana; Cáliz, Rafael; Lupiañez, Carmen B.; Canhão, Helena; Escudero, Alejandro; Segura-Catena, Juana; Soto-Pino, María J.; Ferrer, Miguel A.; García, Antonio; Romani, Lurdes; Pérez-Pampin, Eva; González-Utrilla, Alfonso; López Nevot, Miguel A.; Collantes, Eduardo; Fonseca, João E.; Sainz, Juan
• Is Part Of: Pharmaocogenetics and genomics. Volume 25:Issue 7(2015:Jul.)
• Publication Date: 2015-07
• Subjects: anti-TNF -- drug response -- genetic variants -- rheumatoid arthritis -- susceptibility -- TNFRSF1B/TNFR2; Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000140
• Languages: English
• ISSNs: 1744-6872

Abstract

Abstract : 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 TNFRSF1B rs3397C 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 TNFRSF1B rs1061622 SNP with the risk of RA in the single-SNP analysis ( P =0.89), but also through well-powered meta-analyses ( P DOM =0.67 and P REC =0.37, respectively). In addition, our study showed that carriers of the TNFRSF1B rs3397C/C, TNFRSF1B rs1061622G/G, and TNFRSF1B rs1061631A/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 TNFRSF1B rs3397C or TNFRSF1B rs1061622G alleles showed an increased risk of having worse response to anti-TNF medications ( P= 0.018 and 0.0059). However, the association of the TNFRSF1B rs1061622 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 ( P DOM = 0.12). Conclusion: Our results suggest that the TNFRSF1B rs3397 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. Abstract : Supplemental Digital Content is available in the text.