Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erythematosus in Mexican population.
| Autor: | García-Ortiz H; Genomic of Complex Diseases Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Velázquez-Cruz R, Espinosa-Rosales F, Jiménez-Morales S, Baca V, Orozco L |
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| Jazyk: | angličtina |
| Zdroj: | Annals of the rheumatic diseases [Ann Rheum Dis] 2010 Oct; Vol. 69 (10), pp. 1861-5. Date of Electronic Publication: 2010 Jun 04. |
| DOI: | 10.1136/ard.2009.124313 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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