Show simple item record

dc.contributor.authorGupta, Amitaen_US
dc.contributor.authorMontepiedra, Graceen_US
dc.contributor.authorGupte, Akshayen_US
dc.contributor.authorZeldow, Breten_US
dc.contributor.authorJubulis, Jenniferen_US
dc.contributor.authorDetrick, Barbaraen_US
dc.contributor.authorViolari, Avyen_US
dc.contributor.authorMadhi, Shabiren_US
dc.contributor.authorBobat, Raziyaen_US
dc.contributor.authorCotton, Marken_US
dc.contributor.authorMitchell, Charlesen_US
dc.contributor.authorSpector, Stephenen_US
dc.date.accessioned2016-03-01T19:49:58Z
dc.date.issued2016en_US
dc.identifier.citationGupta, A., G. Montepiedra, A. Gupte, B. Zeldow, J. Jubulis, B. Detrick, A. Violari, et al. 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. doi:10.1371/journal.pone.0148649. http://dx.doi.org/10.1371/journal.pone.0148649.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:25658483
dc.description.abstractBackground: 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 (<32ng/mL). By 192 weeks, 138 incident TB cases (43 definite/probable, and 95 possible) and 26 deaths occurred. Adjusting for HIV status and potential confounders, low 25-hydroxyvitamin D was associated with any TB (adjusted hazard ratio [aHR] 1.76, 95% CI 1.01–3.05; p = 0.046) and any TB or death (aHR 1.76, 95% CI 1.03–3.00; p = 0.038). Children with low 25-hydroxyvitamin D and TMEM 16J rs7111432-AA or PKP3 rs10902158-GG were at increased risk for probable/definite TB or death (aHR 8.12 and 4.83, p<0.05) and any TB or death (aHR 4.78 and 3.26, p<0.005) respectively; SNPs in VDBP, VDR, and vitamin D precursor or hydroxylation genes were not. There was significant interaction between low 25-hydroxyvitamin D and, TMEM 16J rs7111432-AA (p = 0.04) and PKP3 rs10902158-GG (p = 0.02) SNPs. Conclusions: Two novel SNPs, thought to be associated with innate immunity, in combination with low vitamin D levels were identified as increasing a young child’s risk of developing TB disease or death. Identifying high-risk children and providing targeted interventions such as vitamin D supplementation may be beneficial. Trial Registration ClinicalTrials.gov NCT00080119en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0148649en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752266/pdf/en
dash.licenseLAAen_US
dc.subjectPhysical sciencesen
dc.subjectChemistryen
dc.subjectChemical compoundsen
dc.subjectOrganic compoundsen
dc.subjectVitaminsen
dc.subjectVitamin Den
dc.subjectOrganic chemistryen
dc.subjectMedicine and Health Sciencesen
dc.subjectInfectious Diseasesen
dc.subjectBacterial Diseasesen
dc.subjectTuberculosisen
dc.subjectTropical Diseasesen
dc.subjectPeople and Placesen
dc.subjectPopulation Groupingsen
dc.subjectAge Groupsen
dc.subjectInfantsen
dc.subjectChildrenen
dc.subjectFamiliesen
dc.subjectBiology and Life Sciencesen
dc.subjectOrganismsen
dc.subjectBacteriaen
dc.subjectActinobacteriaen
dc.subjectMycobacterium Tuberculosisen
dc.subjectGeneticsen
dc.subjectHeredityen
dc.subjectGenetic Mappingen
dc.subjectVariant Genotypesen
dc.subjectMedicine and health sciencesen
dc.subjectDiagnostic medicineen
dc.subjectHIV diagnosis and managementen
dc.subjectDiagnostic Medicineen
dc.subjectTuberculosis Diagnosis and Managementen
dc.titleLow Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infantsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorMontepiedra, Graceen_US
dc.date.available2016-03-01T19:49:58Z
dc.identifier.doi10.1371/journal.pone.0148649*
dash.authorsorderedfalse
dash.contributor.affiliatedMontepiedra, Grace


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record