Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants

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. A case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwe...

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Veröffentlicht in:	PloS one 2016-02, Vol.11 (2), p.e0148649-e0148649
Hauptverfasser:	Gupta, Amita, Montepiedra, Grace, Gupte, Akshay, Zeldow, Bret, Jubulis, Jennifer, Detrick, Barbara, Violari, Avy, Madhi, Shabir, Bobat, Raziya, Cotton, Mark, Mitchell, Charles, Spector, Stephen
Format:	Artikel
Sprache:	eng
Schlagworte:	25-Hydroxyvitamin D Adult Analysis Anoctamins Autophagy Biology and Life Sciences Breast feeding Care and treatment Chemiluminescence Children Chromosomes Chronology Cohort Studies Death Development and progression Disease Female Follow-Up Studies Gene Expression Genes Genetic diversity Genetic Predisposition to Disease Genetic variance Health aspects Health risks Health sciences HIV HIV infections HIV Infections - complications HIV Infections - genetics HIV Infections - immunology HIV Infections - mortality HIV patients Human immunodeficiency virus Humans Hydroxylation Immune response Immunity Immunoassay Infant Infants Infections Innate immunity Male Medical diagnosis Medicine Medicine and Health Sciences Membrane Proteins - genetics Membrane Proteins - immunology Mortality Mycobacterium tuberculosis Pediatrics People and Places Phospholipid Transfer Proteins Physical sciences Plakophilins - genetics Plakophilins - immunology Polymorphism, Single Nucleotide Public health Real-Time Polymerase Chain Reaction Receptors, Calcitriol - genetics Receptors, Calcitriol - immunology Receptors, Interleukin-1 - genetics Receptors, Interleukin-1 - immunology Risk Single nucleotide polymorphisms Single-nucleotide polymorphism Supplements Survival Analysis Toll-like receptors Tuberculosis Tuberculosis, Pulmonary - complications Tuberculosis, Pulmonary - genetics Tuberculosis, Pulmonary - immunology Tuberculosis, Pulmonary - mortality Vitamin D Vitamin D - analogs & derivatives Vitamin D - blood Vitamin D - immunology Vitamin D Deficiency - complications Vitamin D Deficiency - genetics Vitamin D Deficiency - immunology Vitamin D Deficiency - mortality Vitamin D receptors Vitamin D-Binding Protein - genetics Vitamin D-Binding Protein - immunology Vitamin deficiency
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Zusammenfassung:	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. 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. Median age at 25-hydroxyvitamin D determination was 8 months; 11% were breastfed, 51% were HIV-infected and 26% had low 25-hydroxyvitamin D (
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0148649