Functional polymorphisms in pre-miR146a and pre-miR499 are associated with systemic lupus erythematosus but not with rheumatoid arthritis or Graves' disease in Mexican patients.

Isidro Alemán-Ávila,Carlos Tovilla-Zárate,Silvia Jiménez-Morales,Mayra Jiménez-Morales,Fausto Sánchez-Muñoz,María Concepción Aguilera-Cartas,Rosa Elda Barbosa-Cobos,Guillermo Valencia-Pacheco,Ricardo F López-Villanueva,Julian Ramírez-Bello,Oscar Peralta-Zaragoza,Dulce Milagro Razo-Blanco Hernández,Olga Beltrán-Ramírez,Yaneli Juárez-Vicuña,Luis M Amezcua-Guerra

doi:10.18632/oncotarget.19621

Abstract

Recently, different microRNA (miRNA) gene polymorphisms have been evaluated in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves’ disease (GD). In the present study, we examined three single-nucleotide polymorphisms (SNPs) located in the pre-miR-146a (rs2910164G/C), pre-miR-196a-2 (rs11614913C/T), and pre-miR-499 (rs3746444A/G) genes. Our study population included 900 Mexican patients with RA, SLE, or GD, as well as 486 healthy control individuals with no family history of inflammatory or autoimmune diseases. Genotyping was performed using TaqMan probes and a 5′ exonuclease assay. None of the investigated SNPs were associated with RA or GD susceptibility under any genetic model (co-dominant, recessive, or dominant). Genotype and allele frequencies of the miR-196a-2 rs11614913C/T polymorphism were similar between SLE cases and controls. In contrast, the miR-146a rs2910164G/C and miR-499 rs3746444A/G polymorphisms were associated with SLE susceptibility. These SNPs were not associated with lupus nephritis (LN). Our results suggest that polymorphisms in miR-146a, miR-196a-2, and miR-499 are not associated with RA or GD susceptibility. This is the first report documenting that the miR-146a rs2910164G/C and miR-499 rs3746444 polymorphisms are associated with SLE susceptibility but not with LN.

Highlights

Autoimmune diseases (AIDs) constitute a heterogeneous group of pathologies characterized by loss of immunological tolerance, production of autoantibodies, and increased expression of cytokines with inflammatory activity [1]
Case-control analysis revealed no association between these three single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) or Graves’ disease (GD) susceptibility, even when using recessive and dominant genetic models (Tables 2-7)
We evaluated the miR-146a rs2910164G/C, miR-196a-2 rs11614913C/T, and miR499 rs3746444A/G polymorphisms with regards to their potential associations with RA, systemic lupus erythematosus (SLE), and GD susceptibility in a sample of Mexican patients

Summary

Introduction

Autoimmune diseases (AIDs) constitute a heterogeneous group of pathologies characterized by loss of immunological tolerance, production of autoantibodies, and increased expression of cytokines with inflammatory activity [1]. In the United States, AIDs affect about 5–8% of the general population, with most showing a higher prevalence in women than in men [2]. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial inflammation, which leads to joint tissue destruction and functional disability [3]. Systemic lupus erythematosus (SLE) is the prototype of a multi-systemic AID, and is characterized by loss of immunological tolerance against self-antigens and production of pathogenic autoantibodies, resulting in damage to multiple organ systems [4]. Graves’ diseases (GD) is an organ-specific AID, in which the major antigenic target is the thyroid-stimulating hormone receptor (TSHR). TSHR-autoantibodies bind to TSHR, mimicking the action of its ligand (TSH) and causing hyperthyroidism [5]

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