Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: a case-control and family study.
Vitamin D receptor (VDR) gene polymorphisms have been implicated in susceptibility to tuberculosis (TB), but reports have been inconsistent. We genotyped the VDR single-nucleotide polymorphisms (SNPs) FokI, BsmI, ApaI, and TaqI in 1139 case patients and control subjects and 382 families from The Gambia, Guinea, and Guinea-Bissau. The transmission-disequilibrium test on family data showed a significant global association of TB with SNP combinations FokI-BsmI-ApaI-TaqI and FokI-ApaI that were driven by the increased transmission to affected offspring of the FokI F and ApaI A alleles in combination. The ApaI A allele was also transmitted to affected offspring significantly more often than expected. Case-control analysis showed no statistically significant association between TB and VDR variants. BsmI, ApaI, and TaqI showed strong linkage disequilibrium. The significance of the family-based associations found between TB and FokI-BsmI-ApaI-TaqI and the FA haplotype supports a role for VDR haplotypes, rather than individual genotypes, in susceptibility to TB.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. lbo@na.rau.ac.za.
Liza
L
Bornman
Sarah J
SJ
Campbell
Katherine
K
Fielding
Boubacar
B
Bah
Jackson
J
Sillah
Per
P
Gustafson
Kebba
K
Manneh
Ida
I
Lisse
Angela
A
Allen
Giorgio
G
Sirugo
Aissatou
A
Sylla
Peter
P
Aaby
Keith P W J
KP
McAdam
Oumou
O
Bah-Sow
Steve
S
Bennett
Christian
C
Lienhardt
Adrian V S
AV
Hill
D000328:Adult; D000354:Africa, Western; D016022:Case-Control Studies; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D018562:Disease Transmission, Infectious; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics*
D018167:Receptors, Calcitriol; D004247:DNA; C053864:endodeoxyribonuclease BsmI; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific; C038485:GGGCCC-specific type II deoxyribonucleases; C027046:TCGA-specific type II deoxyribonucleases