Genetic variants within immune-modulating genes influence the risk of developing rheumatoid arthritis and anti-TNF drug response
| Autor: | João Eurico Fonseca, Alejandro Escudero, Miguel Ángel López Nevot, Alfonso González-Utrilla, I. Filipescu, Carmen Belén Lupiañez, L. M. Canet, Juan Sainz, María José Soto-Pino, Manuel Martínez, Juana Segura-Catena, Lurdes Romani, Eva Perez-Pampin, Miguel Ferrer, Eduardo Collantes, Rafael Cáliz, Antonio García, Helena Canhão |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Single-nucleotide polymorphism Disease Biology Polymorphism Single Nucleotide Receptors Interleukin-8B White People Arthritis Rheumatoid Interferon-gamma Genotype Genetics medicine Humans Genetic Predisposition to Disease General Pharmacology Toxicology and Pharmaceutics Allele Molecular Biology Genetics (clinical) Aged Autoimmune disease Case-control study Odds ratio Middle Aged medicine.disease Case-Control Studies Rheumatoid arthritis Immunology Regression Analysis Molecular Medicine Female Interleukin-4 Immunosuppressive Agents |
| Zdroj: | Pharmacogenetics and Genomics. 25:432-443 |
| ISSN: | 1744-6872 |
| DOI: | 10.1097/fpc.0000000000000155 |
| Popis: | 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: | OpenAIRE |
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