Copy number variation in the susceptibility to systemic lupus erythematosus

Autor(es):Mostrar menos -

Barbosa, Fernanda Bueno ^[1] ; Simioni, Milena ^[2] ; Vieira Wiezel, Claudia Emilia ^[1] ; Torres, Fabio Rossi ^[2] ; Molck, Miriam Coelho ^[2] ; Bonilla, Melvin M. ^[3] ; de Araujo, Tabia Kawasaki ^[2] ; Donadi, Eduardo Antonio ^[4] ; Gil-da-Silva-Lopes, Vera Lucia ^[2] ; Lemos, Bernardo ^[3] ; Simoes, Aguinaldo Luiz ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[2] Univ Estadual Campinas, Dept Med Genet, Fac Med Sci, Campinas, SP - Brazil

^[3] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA - USA

^[4] Univ Sao Paulo, Dept Med, Div Clin Immunol, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 13, n. 11 NOV 28 2018.
• Citações Web of Science: 4

Resumo

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. (AU)

• Processo FAPESP: 11/23794-7 - Abordagem investigativa em fendas labiopalatais e cardiopatias congênitas relacionadas à síndrome de deleção 22q11.2 por meio das técnicas de open array e aGH
• Beneficiário: Vera Lúcia Gil da Silva Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/17062-9 - Análise de CNVs em pacientes com Lúpus Eritematoso Sistêmico
• Beneficiário: Fernanda Bueno Barbosa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/10306-8 - Impacto da variação do número de cópias do gene C4 na susceptibilidade ao lúpus eritematoso sistêmico
• Beneficiário: Fernanda Bueno Barbosa
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado