A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseasesopen access
- Authors
- 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.
- Issue Date
- Mar-2017
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE GENETICS, v.49, no.3, pp.433 - 437
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE GENETICS
- Volume
- 49
- Number
- 3
- Start Page
- 433
- End Page
- 437
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4276
- DOI
- 10.1038/ng.3782
- ISSN
- 1061-4036
- Abstract
- Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type 1 interferon signatures. 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 lmmunochip 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(2), predisposes to SLE (odds ratio (OR) = 3.47 in Asians (P-meta = 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.
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