Copy number variation in the susceptibility to systemic lupus erythematosus

• Published in: PloS one 2018-11, Vol.13 (11), p.e0206683
• Main Authors: Barbosa, Fernanda Bueno, Simioni, Milena, Wiezel, Cláudia Emília Vieira, Torres, Fábio Rossi, Molck, Miriam Coelho, Bonilla, Melvin M, de Araujo, Tânia Kawasaki, Donadi, Eduardo Antônio, Gil-da-Silva-Lopes, Vera Lúcia, Lemos, Bernardo, Simões, Aguinaldo Luiz
• Format: Article
• Language: English
• Subjects: ADAM Proteins - genetics; Adult; Age; Antibodies; Apolipoproteins - genetics; Arthritis; Autoantibodies; Autoimmune diseases; Autoimmunity; Biology and Life Sciences; Brazil; Case-Control Studies; Chronic conditions; Cohort Studies; Complement System Proteins - genetics; Copy number; Copy number variations; Deoxyribonucleic acid; Disease; Disease susceptibility; DNA; DNA Copy Number Variations; Environmental health; Ethics; Etiology; Etiology (Medicine); Fc receptors; Female; Gene deletion; Gene expression; Genes; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetic testing; Genetics; Genomes; Genomics; GPI-Linked Proteins - genetics; Health care; High definition television; Histocompatibility antigen HLA; Humans; Inflammation; Loci; Lupus; Lupus erythematosus; Lupus Erythematosus, Systemic - genetics; Male; Medical research; Medical schools; Medicine and Health Sciences; Methods; Mutation; Novels; Patients; People and places; Protective Factors; Public health; Receptors, IgG - genetics; Regression analysis; Regression models; Research and Analysis Methods; Rheumatology; Risk factors; Sex Factors; Synergistic effect; Systemic lupus erythematosus
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0206683

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic component and etiology characterized by chronic inflammation and autoantibody production. The purpose of this study was to ascertain copy number variation (CNV) in SLE using a case-control design in an admixed Brazilian population. The whole-genome detection of CNV was performed using Cytoscan HD array in SLE patients and healthy controls. The best CNV candidates were then evaluated by quantitative real-time PCR in a larger cohort or validated using droplet digital PCR. Logistic regression models adjusted for sex and ancestry covariates was applied to evaluate the association between CNV with SLE susceptibility. The data showed a synergistic effect between the FCGR3B and ADAM3A loci with the presence of deletions in both loci significantly increasing the risk to SLE (5.9-fold) compared to the deletion in the single FCGR3B locus (3.6-fold). In addition, duplications in these genes were indeed more frequent in healthy subjects, suggesting that high FCGR3B/ADAM3A gene copy numbers are protective factors against to disease development. Overall, 21 rare CNVs were identified in SLE patients using a four-step pipeline created for identification of rare variants. Furthermore, heterozygous deletions overlapping the CFHR4, CFHR5 and HLA-DPB2 genes were described for the first time in SLE patients. Here we present the first genome-wide CNV study of SLE patients in a tri-hybrid population. The results show that novel susceptibility loci to SLE can be found once the distribution of structural variants is analyzed throughout the whole genome.