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% 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.
Olesen
R
R
MRC Laboratories, Banjul, The Gambia.
Wejse
C
C
Velez
D R
DR
Bisseye
C
C
Sodemann
M
M
Aaby
P
P
Rabna
P
P
Worwui
A
A
Chapman
H
H
Diatta
M
M
Adegbola
R A
RA
Hill
P C
PC
Østergaard
L
L
Williams
S M
SM
Sirugo
G
G
D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006169:Guinea-Bissau; D006239:Haplotypes; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009169:Mycobacterium tuberculosis; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000378:metabolism; D000099153:Pentraxins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D002097:C-Reactive Protein; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D018167:Receptors, Calcitriol; D011956:Receptors, Cell Surface; D000683:Serum Amyloid P-Component; D051193:Toll-Like Receptors; D000099153:Pentraxins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin