Details

Autor(en) / Beteiligte

• Zhao, Jian
• Ma, Jianyang
• Deng, Yun
• Kelly, Jennifer A
• Kim, Kwangwoo
• Bang, So-Young
• Lee, Hye-Soon
• Li, Quan-Zhen
• Wakeland, Edward K
• Qiu, Rong
• Liu, Mengru
• Guo, Jianping
• Li, Zhanguo
• Tan, Wenfeng
• Rasmussen, Astrid
• Lessard, Christopher J
• Sivils, Kathy L
• Hahn, Bevra H
• Grossman, Jennifer M
• Kamen, Diane L
• Gilkeson, Gary S
• Bae, Sang-Cheol
• Gaffney, Patrick M
• Shen, Nan
• Tsao, Betty P

Titel

A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases

Ist Teil von

• Nature genetics, 2017-03, Vol.49 (3), p.433-437

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 p47 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 (P = 3.1 × 10 ), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjögren'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.