Low vitamin-D levels combined with PKP3-SIGIRR-TMEM16J host variants is associated with tuberculosis and death in HIV-infected and-exposed infants

Amita Gupta, Grace Montepiedra, Akshay Gupte, Bret Zeldow, Jennifer Jubulis, Barbara Detrick, Avy Violari, Shabir Madhi, Raziya Bobat, Mark Cotton, Charles D Mitchell, Stephen Spector

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7 Scopus citations

Abstract

Background: This study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children. Methods: A case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.g. vitamin D receptor (VDR)], vitamin D levels [e.g. vitamin D binding protein (VDBP)], or toll like receptor (TLR) expression (SIGIRR including adjacent genes PKP3 and TMEM16J) were identified by real-time PCR. Outcomes were time to TB, and to the composite of TB or death by 192 weeks of follow-up. Effect modification between vitamin D status and SNPs for outcomes was assessed. Findings: Median age at 25-hydroxyvitamin D determination was 8 months; 11% were breastfed, 51% were HIV-infected and 26% had low 25-hydroxyvitamin D (

Original languageEnglish (US)
Article numbere0148649
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Gupta, A., Montepiedra, G., Gupte, A., Zeldow, B., Jubulis, J., Detrick, B., Violari, A., Madhi, S., Bobat, R., Cotton, M., Mitchell, C. D., & Spector, S. (2016). Low vitamin-D levels combined with PKP3-SIGIRR-TMEM16J host variants is associated with tuberculosis and death in HIV-infected and-exposed infants. PLoS One, 11(2), [e0148649]. https://doi.org/10.1371/journal.pone.0148649