Author: Zhao, J.; Ma, J.; Deng, Y.; Kelly, J.A.; Kim, K.; Bang, S.-Y.; Lee, H.-S.; Li, Q.-Z.; Wakeland, E.K.; Qiu, R.; Liu, M.; Guo, J.; Li, Z.; Tan, W.; Rasmussen, A.; Lessard, C.J.; Sivils, K.L.; Hahn, B.H.; Grossman, J.M.; Kamen, D.L.; Gilkeson, G.S.; Bae, S.-C.; Gaffney, P.M.; Shen, N.; Tsao, B.P.
Description: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production, predisposes to SLE (odds ratio (OR) = 3.47 in Asians (Pmeta = 3.1 x 10-104), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjogren’s syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.
Subject headings: Systemic lupus erythematosus; Autoimmune diseases
Publication year: 2017
Journal or book title: Nature Genetics
Volume: 49
Issue: 3
Pages: 433-437
Find the full text : https://www.nature.com/articles/ng.3782
Find more like this one (cited by): https://scholar.google.com/scholar?cites=911962204946390986&as_sdt=1000005&sciodt=0,16&hl=en
Type: Journal Article
Serial number: 1768