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Ann Rheum Dis. 2010 Oct;69(10):1861-5. doi: 10.1136/ard.2009.124313. Epub 2010 Jun 4.

Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erythematosus in Mexican population.

Author information

1
Genomic of Complex Diseases Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.

Abstract

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.

PMID:
20525845
DOI:
10.1136/ard.2009.124313
[Indexed for MEDLINE]

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