Details:

Alternative Title:
PLoS One
Publisher's site:
http://dx.doi.org/10.1371/journal.pone.0180916
Personal Author:
Magee, Matthew J. ; Sun, Yan V. ; Brust, James C. M. ; Shah, N. Sarita ; Ning, Yuming ; ... More +
Magee, Matthew J. ; Sun, Yan V. ; Brust, James C. M. ; Shah, N. Sarita ; Ning, Yuming ; Allana, Salim ; Campbell, Angela ; Hui, Qin ; Mlisana, Koleka ; Moodley, Pravi ; Gandhi, Neel R. ; Less -
Description:
Background Vitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established. We aimed to determine if SNPs in the VDR gene were associated with sputum culture conversion among a cohort of MDR TB patients in South Africa. Methods We conducted a prospective cohort study of adult MDR TB patients receiving second-line TB treatment in KwaZulu-Natal province. Subjects had monthly sputum cultures performed. In a subset of participants, whole blood samples were obtained for genomic analyses. Genomic DNA was extracted and genotyped with Affymetrix Axiom Pan-African Array. Cox proportional models were used to determine the association between VDR SNPs and rate of culture conversion. Results Genomic analyses were performed on 91 MDR TB subjects enrolled in the sub-study; 60% were female and median age was 35 years (interquartile range [IQR] 29–42). Smoking was reported by 21% of subjects and most subjects had HIV (80%), were smear negative (57%), and had cavitary disease (55%). Overall, 87 (96%) subjects initially converted cultures to negative, with median time to culture conversion of 57 days (IQR 17–114). Of 121 VDR SNPs examined, 10 were significantly associated (p<0.01) with rate of sputum conversion in multivariable analyses. Each additional risk allele on SNP rs74085240 delayed culture conversion significantly (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.67). Conclusions Polymorphisms in the VDR gene were associated with rate of sputum culture conversion in MDR TB patients in this high HIV prevalence setting in South Africa.
Subject:
[+]
Female
HIV Infections
Humans
Male
Polymorphism, Single Nucleotide
Proportional Hazards Models
Prospective Studies
Receptors, Calcitriol
Sputum
Tuberculosis, Multidrug-Resistant
Vitamin D

Source:
PLoS One. 12(7). ;
Pubmed ID:
28700743
Pubmed Central ID:
PMC5507304
Document Type:
Journal Article ;
Place as Subject:
South Africa ;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:b443b2cbbb09f46cda2254d35c951b3c855d07dd0d0c4c93c0ee1c542f332514
File Type:

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