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Low Vitamin-D levels combined with PKP3-SIGIRR-TMEM16J host variants is strongly associated with tuberculosis and death in HIV-infected and -exposed infants
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.
Gupta A, Montepiedra G, Gupte A, Jubulis J, Zeldow B, Detrick B, Violari A, Madhi SA, Bobat R, Cotton MF, Mitchell C, Spector SA, for the IMPAACT NWCS113 and P1041 Study Team. Low Vitamin-D levels combined with PKP3-SIGIRR-TMEM16J host variants is strongly associated with tuberculosis and death in HIV-infected and -exposed infants. PLOS ONE. 2016 Feb 12;11(2):e0148649. doi: 10.1371/journal.pone.0148649. eCollection 2016