<p>ADAM17 Genetic Variants and the Response of TNF-α Inhibitor in Rheumatoid Arthritis Patients</p>

Abstract

TNF-α is a transmembrane protein which requires cleavage by ADAM17 in order to act systemically. The activation of ADAM17 to generate soluble TNF-α 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 TNF-α inhibitors. Patients and Methods: Seven single-nucleotide polymorphisms (SNPs) of ADAM17 in 63 patients with rheumatoid arthritis who received TNF-α 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-α inhibitors. Results: ADAM17 rs117645314 and rs117179141 showed significant association with the number of changes in TNF-α inhibitors. Patients with GA in rs117645314 and AT in rs117179141 had significantly higher chance of two or more changes of TNF-α inhibitors than those with wild homozygous alleles. Multivariate analysis showed that rs117179141 explained 5.7% of the 23.8% variability in TNF-α inhibitor response. Conclusion: This study showed that the number of changes in TNF-α inhibitor is associated with ADAM17 SNPs.

SARS‐CoV‐2, periodontal pathogens, and host factors: The trinity of oral post‐acute sequelae of COVID‐19

“…Furthermore, ADAM17 is the main enzyme responsible for the proteolysis, subsequent activation of pro-TNFα, and release of TNFα from the transmembrane (Table 1). [90][91][92][93] TNFα contributes to the onset and progression of inflammation in both periodontitis and COVID-19. 94 Because hyperinflammation is implicated in SARS-CoV-2-driven organ damage, PS-driven ACE2 ECD and pro-inflammatory cytokine release via ADAM17 may worsen clinical outcomes.…”

ADAM17, A Key Player of Cardiac Inflammation and Fibrosis in Heart Failure Development During Chronic Catecholamine Stress

“…Physiologically, ADAMs and their related metalloenzymes are widely expressed in various body tissues and regulate diverse cellular activities, including cell migration, adhesion, proteolysis, and cellular signaling ( Black et al, 1997 ; Jones et al, 2016 ). Hence, it is not astonishing that alterations in the expression or function of these proteases are implicated in several pathologies, including cancer, rheumatoid arthritis, kidney fibrosis, diabetes, Alzheimer’s disease, and cardiovascular diseases ( Sandgren et al, 1990 ; Black et al, 1997 ; Satoh et al, 2000 ; Umemura et al, 2014 ; Kefaloyianni et al, 2016 ; Zhang et al, 2016 ; Kim et al, 2020 ; Shalaby et al, 2020 ; Adu-Amankwaah et al, 2021a ). Increasing evidence suggests that various ADAMs and other related metalloenzymes play crucial roles in cardiovascular pathophysiology via the modulation of inflammation, angiogenesis, metabolism, cell proliferation, and cell migration ( Adu-Amankwaah et al, 2021a ; Kawai et al, 2021 ).…”

Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population

“…The pro-TNF-α is first synthesized as a type II transmembrane protein and then released soluble TNF-α by ADAM17 [ 5 ]. The activation of ADAM17 promotes the secretion of soluble TNF-α, which increases inflammatory activity [ 6 ]. TNF-α is a representative pro-inflammatory cytokine that plays a critical role in the pathogenesis of inflammatory diseases, such as asthma and allergic inflammation [ 7 , 8 ].…”