Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production

Annals of the Rheumatic Diseases
Yun DengBetty P Tsao

Abstract

Following up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150 kb flanking regions containing NMNAT2 and SMG7 in a 15 292 case-control multi-ancestry population and tested functions of identified variants. We performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10-8, OR=1.23 (95% CI 1.14 to 1.32)). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus (eQTL) datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 patients with SLE and 119 controls (p=1.1×10-3 and 6.8×10-8, respectively) and conferred reduce...Continue Reading

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Citations

Oct 26, 2016·Journal of Autoimmunity·Maria Teruel, Marta E Alarcón-Riquelme
Sep 1, 2017·Journal of Human Genetics·Jae-Jung KimUNKNOWN Korean Kawasaki Disease Genetics Consortium
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May 27, 2016·Current Opinion in Rheumatology·Maria Teruel, Marta E Alarcón-Riquelme
Jan 8, 2021·Annals of the Rheumatic Diseases·Akari SuzukiKazuhiko Yamamoto

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