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

Genes Immun. 2007 Sep;8(6):456-67. doi: 10.1038/sj.gene.6364410. Epub 2007 Jul 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • C-Reactive Protein / genetics*
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Guinea-Bissau
  • Haplotypes
  • Humans
  • Lectins, C-Type / genetics*
  • Lectins, C-Type / metabolism
  • Male
  • Mycobacterium tuberculosis
  • Polymorphism, Single Nucleotide*
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / metabolism
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Serum Amyloid P-Component / genetics*
  • Serum Amyloid P-Component / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Tuberculosis, Pulmonary / genetics
  • Tuberculosis, Pulmonary / metabolism

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Calcitriol
  • Receptors, Cell Surface
  • Serum Amyloid P-Component
  • Toll-Like Receptors
  • PTX3 protein
  • C-Reactive Protein