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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.

Original publication

DOI

10.1086/424462

Type

Journal article

Journal

J Infect Dis

Publication Date

01/11/2004

Volume

190

Pages

1631 - 1641

Keywords

Adult, Africa, Western, Case-Control Studies, DNA, Deoxyribonucleases, Type II Site-Specific, Disease Transmission, Infectious, Female, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Calcitriol, Tuberculosis