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Single nucleotide polymorphisms in genes encoding toll-like receptors 7, 8 and 9 in Danish patients with systemic lupus erythematosus

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Abstract

Several studies indicate a role for toll-like receptors (TLRs) in the pathogenesis of systemic lupus erythematosus (SLE). We aimed to investigate the risk of SLE and typical clinical and serological manifestations of SLE potentially conferred by selected single nucleotide polymorphisms (SNPs) of genes encoding TLR7, TLR8, and TLR9. Using a multiplexed bead-based assay, we analyzed eight SNPs in a cohort of 142 Danish SLE patients and a gender-matched control cohort comprising 443 individuals. Our results showed an association between the rs3853839 polymorphism of TLR7 and SLE (G vs. C, P = 0.008, OR 1.60, 95 % CI 1.12–2.27 in females; P = 0.02, OR 4.50, 95 % CI 1.18–16.7 in males) confirming recent findings in other populations. Additionally, an association between the rs3764879 polymorphism of TLR8 and SLE (G vs. C, P < 0.05, OR 1.36, 95 % CI 0.99–1.86 in females; P = 0.06, OR 4.00, 95 % CI 0.90–17.3 in males) was found. None of the other investigated SNPs were associated with SLE but several SNPs were associated with clinical and serological manifestations. In summary, a previously shown association between the rs3853839 SNP of TLR7 and SLE in Asian patients was also found in Danish patients. Together with the association of several other SNPs of TLR8 and TLR9 with various clinical and serological manifestations of SLE these findings corroborate the pathogenic significance of TLRs in SLE.

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Acknowledgments

We thank Pia Grothe Meinke for technical assistance. We also thank all patients and healthy control subjects for their participation. The Danish Biotechnology Program, Novo Nordisk Foundation, The Danish Rheumatism Association, and The Lundbeck Foundation are thanked for financial support. The Copenhagen Aging and Midlife Biobank has been supported by a generous grant from the VELUX FOUNDATION. The authors wish to thank Prof. Palle Holmstrup for establishing and making possible the project that enabled genotyping of the control samples from the CAMB cohort used herein. The authors thank the staff at the Institute of Public Health and the National Research Center for the Working Environment who undertook the data collection. Further thanks to Helle Bruunsgaard, Nils-Erik Fiehn, Åse Marie Hansen, Poul Holm-Pedersen, Rikke Lund, Erik Lykke Mortensen and Merete Osler who initiated and established the Copenhagen Aging and Midlife Biobank from 2009 to 2011 together with Kirsten Avlund. The authors acknowledge the crucial role of the initiators and steering groups of the Metropolit Cohort, The Copenhagen Perinatal Cohort and The Danish Longitudinal Study on Work Unemployment and Health.

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Authors and Affiliations

  1. Institute for Inflammation Research, Department of Infectious Medicine and Rheumatology, Rigshospitalet, Copenhagen, Denmark

    C. Enevold, C. H. Nielsen, R. S. Jacobsen, M. L. F. Hermansen, K. Bendtzen & S. Jacobsen

  2. Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    D. Molbo & K. Avlund

  3. Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark

    K. Avlund

  4. Danish Aging Research Center, University of Aarhus, Aarhus, Denmark

    K. Avlund

  5. Danish Aging Research Center, University of Southern Denmark, Odense, Denmark

    K. Avlund

  6. Danish Aging Research Center, University of Copenhagen, Copenhagen, Denmark

    K. Avlund

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  1. C. Enevold
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Enevold, C., Nielsen, C.H., Jacobsen, R.S. et al. Single nucleotide polymorphisms in genes encoding toll-like receptors 7, 8 and 9 in Danish patients with systemic lupus erythematosus. Mol Biol Rep 41, 5755–5763 (2014). https://doi.org/10.1007/s11033-014-3447-4

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