Genetic variants within immune-modulating genes influence the risk of developing rheumatoid arthritis and anti-TNF drug response. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Canet, Luz M.; Cáliz, Rafael; Lupiañez, Carmen B.; Canhão, Helena; Martinez, Manuel; Escudero, Alejandro; Filipescu, Ileana; Segura-Catena, Juana; Soto-Pino, María J.; Ferrer, Miguel A.; García, Antonio; Romani, Lurdes; Pérez-Pampin, Eva; González-Utrilla, Alfonso; López Nevot, Miguel Ángel; Collantes, Eduardo; Fonseca, João E.; Sainz, Juan
• Is Part Of: Pharmaocogenetics and genomics. Volume 25:Issue 9(2015:Sep.)
• Publication Date: 2015-09
• Subjects: Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000155
• Languages: English
• ISSNs: 1744-6872

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>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.</p> </sec> <sec> <title>Materials and methods</title> <p>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.</p> </sec> <sec> <title>Results</title> <p>Logistic regression analyses showed that carriers of the <italic>IL4</italic><sub>rs2070874T</sub> and <italic>IL4</italic><sub>rs2243250T</sub> and <italic>IL8RB</italic><sub>rs1126580A</sub> alleles or the <italic>IL8RB</italic><sub>rs2230054C/C</sub> genotype had a significantly increased risk of developing RA [odds ratio (OR)=1.37, 95% confidence interval (CI) 1.13–1.67, <italic>P</italic>=0.0016; OR=1.24, 95% CI 1.03–1.49, <italic>P</italic>=0.020; OR=1.23, 95% CI 1.08–1.41, <italic>P</italic>=0.002 and OR=1.19, 95% CI 1.04–1.36, <italic>P</italic>=0.01, respectively]. The association of the <italic>IL4</italic> variants was further supported by a meta-analysis including 7150 individuals (<italic>P</italic> =0.0010), whereas the involvement of the <italic>IL8RB</italic> 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 <italic>IL8RB</italic> variants that act synergistically to increase the risk of the disease (<italic>P</italic>=0.014 and 0.018). Interestingly, we also found that patients harbouring the <italic>IFNG</italic><sub>rs2069705C</sub> allele showed a significantly better response to anti-TNF drugs than those patients carrying the wild-type allele (<italic>P</italic>=0.0075).</p> </sec> <sec> <title>Conclusions</title> <p>Our data suggest that <italic>IL4</italic> and <italic>IL8RB</italic> loci may have a small-effect genetic impact on the risk of developing RA, whereas <italic>IFNG</italic> might be involved in modulating the response to anti-TNF drugs.</p> </sec> </abstract>