The AIRE Ser196Ser synonymous variant is a risk factor for systemic lupus erythematosus

• Published in: Cellular immunology 2019-12, Vol.346, p.103986-103986, Article 103986
• Main Authors: Montufar-Robles, Isela, Robles-Garnica, José Carlos, Cadena-Sandoval, Daniel, Barbosa-Cobos, Rosa Elda, González-Castillo, Daniel David, Romero-Diaz, Juanita, Sánchez-Muñoz, Fausto, Saavedra, Miguel A., Olivares-Martínez, Elizabeth, Miranda-Hernández, Dafhne, Ramírez-Bello, Julian
• Format: Article
• Language: English
• Subjects: AIRE; AIRE Protein; Arthritis, Rheumatoid - genetics; Case-Control Studies; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; Humans; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Nephritis - genetics; Mexico; Polymorphism, Single Nucleotide - genetics; Risk Factors; Single nucleotide variant Susceptibility; Systemic lupus erythematosus; T-Lymphocytes - immunology; Transcription Factors - genetics
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2019.103986

•We performed a study involving 379 healthy controls and 460 patients with SLE.•Our data showed that the AIRE Ser196Ser (rs878081C/T) synonymous variant was associated with SLE. Our results suggest that AIRE is a risk factor for SLE.•In addition, we replicated our finding in another group of 179 SLE patients and 97 controls from the same region of Mexico.•This study is the first to document an association between AIRE and SLE susceptibility. The AIRE gene influences the expression of a wide array of self-antigens in the thymus, and is essential to the negative selection of self-reactive T cells and establishment of central tolerance. Single nucleotide variants (SNVs) such as rs878081C/T (Ser196Ser) and rs2075876G/T at this locus have been associated with susceptibility to rheumatoid arthritis, mainly in Asian populations, but its role in systemic lupus erythematosus (SLE) has not been documented. We performed a case-control association study with 379 SLE patients and 460 controls from central Mexico. In addition, we replicated our finding in another group of 179 SLE patients and 97 controls from the same region of Mexico. In the first group, we identified that the AIRE Ser196Ser synonymous variant was associated with SLE (OR 1.4, p = 0.009), meanwhile, in the second group we observed the following: OR 1.7, p = 0.024. No association was found between these AIRE SNVs and lupus nephritis. Our results suggest that AIRE is a risk factor for SLE in our population. This study is the first to document an association between AIRE and SLE susceptibility.