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Association of systemic lupus erythematosus (SLE) genetic susceptibility loci with lupus nephritis in childhood-onset and adult-onset SLE.
Webber, Declan; Cao, Jingjing; Dominguez, Daniela; Gladman, Dafna D; Levy, Deborah M; Ng, Lawrence; Paterson, Andrew D; Touma, Zahi; Urowitz, Murray B; Wither, Joan E; Silverman, Earl D; Hiraki, Linda T.
Afiliação
  • Webber D; Division of Rheumatology, Department of Pediatrics, University of Toronto, Toronto, Canada.
  • Cao J; Genetics & Genome Biology, Research Institute, SickKids Hospital, Toronto, Canada.
  • Dominguez D; Division of Rheumatology, Department of Pediatrics, University of Toronto, Toronto, Canada.
  • Gladman DD; Krembil Research Institute, Toronto Western Hospital, Toronto, Canada.
  • Levy DM; Division of Rheumatology, Department of Pediatrics, University of Toronto, Toronto, Canada.
  • Ng L; Division of Rheumatology, Department of Pediatrics, University of Toronto, Toronto, Canada.
  • Paterson AD; Genetics & Genome Biology, Research Institute, SickKids Hospital, Toronto, Canada.
  • Touma Z; Krembil Research Institute, Toronto Western Hospital, Toronto, Canada.
  • Urowitz MB; Krembil Research Institute, Toronto Western Hospital, Toronto, Canada.
  • Wither JE; Krembil Research Institute, Toronto Western Hospital, Toronto, Canada.
  • Silverman ED; Division of Rheumatology, Department of Pediatrics, University of Toronto, Toronto, Canada.
  • Hiraki LT; Division of Translational Medicine Research Institute, Toronto, Canada.
Rheumatology (Oxford) ; 59(1): 90-98, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31236574
ABSTRACT

OBJECTIVE:

LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE).

METHODS:

Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed.

RESULTS:

Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002).

CONCLUSION:

We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Nefrite Lúpica / Idade de Início / Predisposição Genética para Doença / Loci Gênicos / Lúpus Eritematoso Sistêmico Limite: Adolescente / Adulto / Criança / Feminino / Humanos / Masculino / Jovem adulto Idioma: Inglês Revista: Rheumatology (Oxford) Assunto da revista: Reumatologia Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Canadá

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Nefrite Lúpica / Idade de Início / Predisposição Genética para Doença / Loci Gênicos / Lúpus Eritematoso Sistêmico Limite: Adolescente / Adulto / Criança / Feminino / Humanos / Masculino / Jovem adulto Idioma: Inglês Revista: Rheumatology (Oxford) Assunto da revista: Reumatologia Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Canadá
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