OBJECTIVES: A single nucleotide polymorphism in the NCF1 gene (NCF1-339, rs201802880), encoding NADPH oxidase type II subunit NCF1/p47<sup>phox</sup>, reducing production of reactive oxygen species (ROS) is strongly associated with the development of systemic lupus erythematosus (SLE).
Genome-wide association studies of systemic lupus erythematosus (SLE) in Chinese and Korean populations demonstrated strong association of single nucleotide polymorphisms (SNPs) located in the GTF2I-NCF1 region, rs73366469 (GTF2I), rs117026326 (GTF2I), rs80346167(GTF2IRD1) and rs201802880 (NCF1).
We aimed at investigating association and function of the missense single nucleotide polymorphism (SNP), rs201802880 (here denoted NCF1-339) in <i>NCF1</i> with systemic lupus erythematosus (SLE).
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<sub>meta</sub> = 3.1 × 10<sup>-104</sup>), 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).