Article

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

MRC Laboratories, Banjul, The Gambia.
Genes and Immunity (Impact Factor: 3.79). 10/2007; 8(6):456-67. DOI: 10.1038/sj.gene.6364410
Source: PubMed

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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    • "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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    • "Two intronic SNPs (rs2305619 and rs1840680) in PTX3 were associated with APN susceptibility in terms of frequency and odds ratio. These two intronic SNPs have previously been associated with P. aeruginosa colonization in cystic fibrosis patients and increased risk for pulmonary tuberculosis (Chiarini et al., 2010; Olesen et al., 2007), suggesting that these SNPs might increase the risk of bacterial colonization. However, these SNPs increase the risk for APN and cystitis but not general bacterial colonization of the bladder because no association of these SNPs, or other PTX3 SNPs examined here, were observed for the two ABU groups. "
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    • "One mechanism to confer immuno-protection may be mediated by monocytes that are induced to express PTX3 by the mycobacterial component (Mycobacterial lipoarabinomannan, LAM) (Vouret-Craviari et al., 1997). In humans, susceptibility to Mycobacterium tuberculi is also found to be positively associated with two intronic SNPs (rs1840680 and rs2305619) in PTX3 gene (Olesen et al., 2007). "
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