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DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans

Genes & Immunity volume 8, pages 456–467 (2007)Cite this article

Abstract

We investigated the role of DC-SIGN (CD209), long pentraxin 3 (PTX3) and vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) in susceptibility to pulmonary tuberculosis (TB) in 321 TB cases and 347 healthy controls from Guinea-Bissau. Five additional, functionally relevant SNPs within toll-like receptors (TLRs) 2, 4 and 9 were typed but found, when polymorphic, not to affect host vulnerability to pulmonary TB. We did not replicate an association between SNPs in the DC-SIGN promoter and TB. However, we found that two polymorphisms, one in DC-SIGN and one in VDR, were associated in a nonadditive model with disease risk when analyzed in combination with ethnicity (P=0.03 for DC-SIGN and P=0.003 for VDR). In addition, PTX3 haplotype frequencies significantly differed in cases compared to controls and a protective effect was found in association with a specific haplotype (OR 0.78, 95% CI 0.63–0.98). Our findings support previous data showing that VDR SNPs modulate the risk for TB in West Africans and suggest that variation within DC-SIGN and PTX3 also affect the disease outcome.

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Acknowledgements

This study was funded by the MRC award G0000690 to GS, and by Grants from the Danish Medical Research Council, the Danish society of respiratory medicine, the Danish Council of Development Research to RO, CW, MS and LO.

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Author notes

  1. R Olesen and C Wejse: These authors contributed equally to this work.

Authors and Affiliations

  1. MRC Laboratories, Banjul, The Gambia

    R Olesen, C Bisseye, A Worwui, H Chapman, M Diatta, R A Adegbola, P C Hill & G Sirugo

  2. Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark

    R Olesen, C Wejse, M Sodemann & L Østergaard

  3. Bandim Health Project, Danish Epidemiology Science Centre and Statens Serum Institut, Bissau, Guinea-Bissau,

    C Wejse, P Aaby & P Rabna

  4. Department of Cardiovascular Medicine, Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA

    D R Velez & S M Williams

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Correspondence to G Sirugo.

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Olesen, R., Wejse, C., Velez, D. et al. DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun 8, 456–467 (2007). https://doi.org/10.1038/sj.gene.6364410

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