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Extended report
Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erythematosus in Mexican population
  1. Humberto García-Ortiz1,
  2. Rafael Velázquez-Cruz1,
  3. Francisco Espinosa-Rosales2,
  4. Silvia Jiménez-Morales1,
  5. Vicente Baca3,
  6. Lorena Orozco1
  1. 1Genomic of Complex Diseases Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
  2. 2Department of Immunology, Instituto Nacional de Pediatría, Mexico City, Mexico
  3. 3Department of Rheumatology, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
  1. Correspondence to Lorena Orozco, Instituto Nacional de Medicina Genómica, Periférico Sur 4124, Torre Zafiro II, 6º piso, Colonia Jardines del Pedregal, México City, DF, CP 01900, México; lorozco{at}


Objective Variations in gene copy number (CNV) have been recognised as a hereditable source of susceptibility in human complex diseases. Recent studies have shown that Tlr7 gene dosage has a significant contribution in the autoimmune-enhancing effect in mouse models of systemic lupus erythematosus (SLE). A study was therefore performed to investigate whether CNVs in TLR7 contribute to the genetic component of childhood-onset SLE.

Methods A case–control association study was performed in 328 Mexican children with SLE and 403 healthy controls. Determination of CNVs of TLR7 was achieved by real-time PCR using the ΔΔCt method. Expression levels of TLR7 and interferon α (IFNα) were determined in 23 patients. In addition, a stratification analysis was performed to investigate the association of TLR7 gene copy number (CN) with lupus nephritis.

Results A significant increase was found in the relative TLR7 gene CN in females patients with SLE compared with female controls (p<0.0001). However, logistic regression analysis by gender showed a higher OR (OR 6.61, p=0.005) in male patients with >1 copy of TLR7 than in female patients with >2 copies (OR 3.07, p<0.0001). This association was not observed with lupus nephritis. TLR7 mRNA levels correlated significantly with TLR7 CN and with IFNα mRNA levels.

Conclusion These results show that an increase in TLR7 CN is a risk factor for childhood-onset SLE and provide new evidence for a role for X-linked gene dosage in SLE susceptibility. There is also evidence to suggest that TLR7 may be involved in the pathogenesis of SLE through the induction of IFNα.

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  • Funding HGO was funded by the Consejo Nacional de Ciencia y Tecnología (CONACYT), scholarship No 210338. This study was supported by a grant from the CONACYT (SALUD-2004-01-153).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Centro Médico Nacional Siglo XXI and the Instituto Nacional de Medicina Genómica and the Instituto Nacional de Pediatría.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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