Genetic variants within immune-modulating genes influence the risk of developing rheumatoid arthritis and anti-TNF drug response: a two-stage case-control study.
| Autor: | Canet LM; aGenomic Oncology Area bArea of Genomic Medicine, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government Departments of cRheumatology dImmunology, Virgen de las Nieves University Hospital, Granada eDepartment of Rheumatology, Reina Sofía Hospital/Maimónides Institut for Biomedical Research of CórdobaI (IMIBIC)/University of Córdoba, Córdoba fRheumatology Unit, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain gRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa hDepartment of Rheumatology, Santa Maria Hospital-CHLN, Lisbon, Portugal iRheumatology Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Cáliz R, Lupiañez CB, Canhão H, Martinez M, Escudero A, Filipescu I, Segura-Catena J, Soto-Pino MJ, Ferrer MA, García A, Romani L, Pérez-Pampin E, González-Utrilla A, López Nevot MÁ, Collantes E, Fonseca JE, Sainz J |
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| Jazyk: | angličtina |
| Zdroj: | Pharmacogenetics and genomics [Pharmacogenet Genomics] 2015 Sep; Vol. 25 (9), pp. 432-43. |
| DOI: | 10.1097/FPC.0000000000000155 |
| Abstrakt: | Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that arises as a result of the interaction between genetic and environmental factors. A growing body of research suggests that genetic variants within immune-related genes can influence the risk of developing the disease and affect drug response. Materials and Methods: To test this hypothesis, we carried out a comprehensive two-stage case-control study in a White population of 1239 White RA patients and 1229 healthy controls to investigate whether 49 single nucleotide polymorphisms within or near 17 immune-related genes modulate the risk of developing RA and antitumor necrosis factor (anti-TNF) drug response. Results: Logistic regression analyses showed that carriers of the IL4rs2070874T and IL4rs2243250T and IL8RBrs1126580A alleles or the IL8RBrs2230054C/C genotype had a significantly increased risk of developing RA [odds ratio (OR)=1.37, 95% confidence interval (CI) 1.13-1.67, P=0.0016; OR=1.24, 95% CI 1.03-1.49, P=0.020; OR=1.23, 95% CI 1.08-1.41, P=0.002 and OR=1.19, 95% CI 1.04-1.36, P=0.01, respectively]. The association of the IL4 variants was further supported by a meta-analysis including 7150 individuals (P =0.0010), whereas the involvement of the IL8RB locus in determining the susceptibility to RA was also supported by gene-gene interaction analyses that identified significant two-locus and three-locus interaction models including IL8RB variants that act synergistically to increase the risk of the disease (P=0.014 and 0.018). Interestingly, we also found that patients harbouring the IFNGrs2069705C allele showed a significantly better response to anti-TNF drugs than those patients carrying the wild-type allele (P=0.0075). Conclusions: Our data suggest that IL4 and IL8RB loci may have a small-effect genetic impact on the risk of developing RA, whereas IFNG might be involved in modulating the response to anti-TNF drugs. |
| Databáze: | MEDLINE |
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