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

ABSTRACT: 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^phox 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_meta = 3.1 × 10^-104), OR = 2.61 in European Americans, OR = 2.02 in African Americans)

SUBMITTER: Zhao J 

PROVIDER: S-EPMC5400098 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature