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A single nucleotide polymorphism in the NCF1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus
Karolinska Inst, Div Med Inflammat Res, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden..
Lund Univ, Div Hematol & Transfus Med, Dept Lab Med, Fac Med, Lund, Sweden.;Lund Univ, Div Clin Immunol & Transfus Med, Dept Lab Med, Fac Med, Lund, Sweden..
Lund Univ, Dept Clin Sci Lund, Rheumatol, Fac Med, Lund, Sweden..
Lund Univ, Dept Clin Sci Lund, Rheumatol, Fac Med, Lund, Sweden..
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 9, p. 1607-1613Article in journal (Refereed) Published
Abstract [en]

Objectives

Ncf1 polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases in animal models. The human NCF1 gene is very complex with both functional and non-functional gene copies and genotyping requires assays specific for functional NCF1 genes. We aimed at investigating association and function of the missense single nucleotide polymorphism (SNP), rs201802880 (here denoted NCF1-339) in NCF1 with systemic lupus erythematosus (SLE).

Methods

We genotyped the NCF1-339 SNP in 973 Swedish patients with SLE and 1301 controls, using nested PCR and pyrosequencing. ROS production and gene expression of type 1 interferon-regulated genes were measured in isolated cells from subjects with different NCF1-339 genotypes.

Results

We found an increased frequency of the NCF1-339 T allele in patients with SLE, 11% compared with 4% in controls, OR 3.0, 95% CI 2.4 to 3.9, p=7.0x10(-20) The NCF1-339 T allele reduced extracellular ROS production in neutrophils (p=0.004) and led to an increase expression of type 1 interferon-regulated genes. In addition, the NCF1-339 T allele was associated with a younger age at diagnosis of SLE; mean age 30.3 compared with 35.9, p=2.0x1(-6).

Conclusions

These results clearly demonstrate that a genetically controlled reduced production of ROS increases the risk of developing SLE and confirm the hypothesis that ROS regulate chronic autoimmune inflammatory diseases.

Place, publisher, year, edition, pages
2017. Vol. 76, no 9, p. 1607-1613
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:uu:diva-333949DOI: 10.1136/annrheumdis-2017-211287ISI: 000407833100033PubMedID: 28606963OAI: oai:DiVA.org:uu-333949DiVA, id: diva2:1165526
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2017-12-13Bibliographically approved

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Rönnblom, LarsLeonard, Dag

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