DC-SIGN (CD209), Pentraxin 3 and Vitamin D Receptor gene variants associate with pulmonary tubercolosis risk in West-Africans

MRC Laboratories, Banjul, The Gambia.
Genes and Immunity (Impact Factor: 2.91). 10/2007; 8(6):456-67. DOI: 10.1038/sj.gene.6364410
Source: PubMed


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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    • "Mechanistically, PTX3 acts as an opsonin, which not only enhances phagocytosis and killing of pathogens but also promotes dendritic cell maturation and polarization, thereby contributing to the activation of the adaptive immune response (Bottazzi et al., 2010). Intriguingly, polymorphisms in the PTX3 gene are associated with risk for pulmonary tuberculosis and P. aeruginosa infections in cystic fibrosis (Olesen et al., 2007; Chiarini et al., 2010). Furthermore, PTX3 mediates a variety of antiviral activities against influenza viruses, including inhibition of virus-induced hemagglutination and viral neuramidase activity, as well as neutralization of virus infectivity in vitro (Reading et al., 2008). "
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    • "These findings have motivated a large number of linkage and candidate gene association studies seeking to identify relevant susceptibility loci, but results have often been inconclusive or, worse, contradictory. Many biologically plausible genes, such as those that encode vitamin-D-binding protein (Lewis et al., 2005; Gao et al., 2010), the phagolysomal membrane protein NRAMP/SLC11A1 (Hoal et al., 2004; Velez et al., 2009), and the dendritic adhesion molecule DC-SIGN (Barreiro et al., 2006; Olesen et al., 2007), appear to associate with TB in some human populations, but not others. Inconsistent replication across ethnic groups has also beset the handful of GWAS performed on TB (Chimusa et al., 2014). "
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    • "The pulmonary TB data is from a case-control study [30] conducted at The Bandim Health Project (BHP) in Bissau , the capital city of Guinea-Bissau. This area has a high prevalence of pulmonary TB and TB symptoms [4]. "
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