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Meta-Analysis
. 2015 Jul;25(7):323-33.
doi: 10.1097/FPC.0000000000000140.

Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study

Luz M Canet  1 , Ileana Filipescu, Rafael Cáliz, Carmen B Lupiañez, Helena Canhão, Alejandro Escudero, Juana Segura-Catena, María J Soto-Pino, Miguel A Ferrer, Antonio García, Lurdes Romani, Eva Pérez-Pampin, Alfonso González-Utrilla, Miguel A López Nevot, Eduardo Collantes, João E Fonseca, Juan Sainz
Affiliations
Meta-Analysis

Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study

Luz M Canet et al. Pharmacogenet Genomics. 2015 Jul.

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 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.

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