ADAM17 Genetic Variants and the Response of TNF-alpha Inhibitor in Rheumatoid Arthritis Patients

Abstract

PURPOSE: TNF-alpha is a transmembrane protein which requires cleavage by ADAM17 in order to act systemically. The activation of ADAM17 to generate soluble TNFalpha results in an increased inflammatory activity. We hypothesized that variants spanning the ADAM17 gene contribute towards the observed variation in patient response defined by the number of changes in TNFalpha inhibitors. <br>PATIENTS AND METHODS: Seven single-nucleotide polymorphisms (SNPs) of ADAM17 in 63 patients with rheumatoid arthritis who received TNF-alpha inhibitors were analyzed: rs57467365, rs62117540, rs117645314, rs6432013, rs532704607, rs117179141, and rs12692386. Univariate and multivariate regression analysis were employed to investigate the independent predictable factors for changes in TNF-alpha inhibitors. <br>RESULTS: ADAM17 rs117645314 and rs117179141 showed significant association with the number of changes in TNF-alpha inhibitors. Patients with GA in rs117645314 and AT in rs117179141 had significantly higher chance of two or more changes of TNF-alpha inhibitors than those with wild homozygous alleles. Multivariate analysis showed that rs117179141 explained 5.7% of the 23.8% variability in TNF-alpha inhibitor response. <br>CONCLUSION: This study showed that the number of changes in TNF-alpha inhibitor is associated with ADAM17 SNPs.