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dc.contributor.authorAguilar-Jiménez, Wbeimar
dc.contributor.authorZapata, Wildeman
dc.contributor.authorRivero-Juárez, Antonio
dc.contributor.authorPineda, Juan Antonio
dc.contributor.authorLaplana Lafaja, Marina
dc.contributor.authorTaborda, Natalia A.
dc.contributor.authorBiasin, Mara
dc.contributor.authorClerici, Mario
dc.contributor.authorCaruz, Antonio
dc.contributor.authorFibla Palazón, Joan
dc.contributor.authorRugeles, Maía T.
dc.description.abstractVitamin D (VitD) may modulate anti-HIV-1 responses modifying the risk to acquire the HIV-1-infection. We performed a nested case-control exploratory study involving 413 individuals; HIV-1-exposed seropositives (cases) and seronegatives (HESN) (controls) from three cohorts: sexually-exposed from Colombia and Italy and parenterally-exposed from Spain. The association and interactions of 139 variants in 9 VitD pathway genes, and in 14 antiviral genes with resistance/susceptibility (R/S) to HIV-1 infection was evaluated. Associations between variants and mRNA levels were also analyzed in the Colombian samples. Variants and haplotypes in genes of VitD and antiviral pathways were associated with R/S, but specific associations were not reproduced in all cohorts. Allelic heterogeneity could explain such inconsistency since the associations found in all cohorts were consistently in the same genes: VDR and RXRA of the VitD pathway genes and in TLR2 and RNASE4. Remarkably, the multi-locus genotypes (interacting variants) observed in genes of VitD and antiviral pathways were present in most HESNs of all cohorts. Finally, HESNs carrying resistance-associated variants had higher levels of VitD in plasma, of VDR mRNA in blood cells, and of ELAFIN and defensins mRNA in the oral mucosa. In conclusion, despite allelic heterogeneity, most likely due to differences in the genetic history of the populations, the associations were locus dependent suggesting that genes of the VitD pathway might act in concert with antiviral genes modulating the resistance phenotype of the HESNs. Although these associations were significant after permutation test, only haplotype results remained statistically significant after Bonferroni test, requiring further replications in larger cohorts and functional analyzes to validate these conclusions.
dc.description.sponsorshipThis work was supported by Departamento administrativo de ciencia, tecnología e innovación de Colombia, COLCIENCIAS (grant no. 111549326091); Universidad de Antioquia UdeA, Colombia (sostenibilidad); Universidad Cooperativa de Colombia (code INV1900); Consejería de Salud de la Junta de Andalucía (PI-0335/2009, PI-0118-2013, PI-0481-2012, and AC-0095-2013), Gilead (GLDL13-00145), the Ministerio de Sanidad (EC11-2086, PI021476, and PI10/01232), the Red de Investigación en SIDA (ISCIII-RETIC RD06/006 and RD12/0017), the Fundación Maratón TV3 (020730 and 020732) and the Universidad de Jaén (UJA2013/10/03 and UJA2013/08/12).
dc.relation.isformatofVersió postprint del document publicat a:
dc.relation.ispartofInfection Genetics And Evolution, 2019, vol. 73, p. 276-286
dc.rightscc-by-nc-nd, (c) Elsevier, 2019
dc.subjectNatural resistance
dc.subjectVitamin D pathway
dc.subjectAntiviral agents
dc.titleGenetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability

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cc-by-nc-nd, (c) Elsevier, 2019
Except where otherwise noted, this item's license is described as cc-by-nc-nd, (c) Elsevier, 2019