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

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% Cl 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.