Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability
Vitamin 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 Colo...
- Autores:
-
Zapata Builes, Wildeman
Aguilar Jiménez, Wbeimar
Rivero Juárez, Antonio
Pineda, Juan A.
Laplana, Marina
Taborda, Natalia Andrea
Biasin, Mara
Clerici, Mario
Caruz, Antonio
Fibla, Joan
Rugeles López, María Teresa
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2019
- Institución:
- Universidad Cooperativa de Colombia
- Repositorio:
- Repositorio UCC
- Idioma:
- OAI Identifier:
- oai:repository.ucc.edu.co:20.500.12494/15802
- Acceso en línea:
- https://hdl.handle.net/20.500.12494/15802
- Palabra clave:
- HIV-1
Natural resistance
HESN
Vitamin D pathway
Antiviral agents
Epistasis
Allelic heterogeneity
Association study
HIV-1
Natural resistance
HESN
Vitamin D pathway
Antiviral agents
Antiviral agents
Epistasis
Allelic heterogeneity
Association study
- Rights
- openAccess
- License
- Atribución – No comercial – Sin Derivar
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COOPER2_3b2b94383beb61b99ca687108a87a885 |
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| oai_identifier_str |
oai:repository.ucc.edu.co:20.500.12494/15802 |
| network_acronym_str |
COOPER2 |
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Repositorio UCC |
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|
| dc.title.spa.fl_str_mv |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability |
| title |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability |
| spellingShingle |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability HIV-1 Natural resistance HESN Vitamin D pathway Antiviral agents Epistasis Allelic heterogeneity Association study HIV-1 Natural resistance HESN Vitamin D pathway Antiviral agents Antiviral agents Epistasis Allelic heterogeneity Association study |
| title_short |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability |
| title_full |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability |
| title_fullStr |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability |
| title_full_unstemmed |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability |
| title_sort |
Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability |
| dc.creator.fl_str_mv |
Zapata Builes, Wildeman Aguilar Jiménez, Wbeimar Rivero Juárez, Antonio Pineda, Juan A. Laplana, Marina Taborda, Natalia Andrea Biasin, Mara Clerici, Mario Caruz, Antonio Fibla, Joan Rugeles López, María Teresa |
| dc.contributor.author.none.fl_str_mv |
Zapata Builes, Wildeman Aguilar Jiménez, Wbeimar Rivero Juárez, Antonio Pineda, Juan A. Laplana, Marina Taborda, Natalia Andrea Biasin, Mara Clerici, Mario Caruz, Antonio Fibla, Joan Rugeles López, María Teresa |
| dc.subject.spa.fl_str_mv |
HIV-1 Natural resistance HESN Vitamin D pathway Antiviral agents Epistasis Allelic heterogeneity Association study |
| topic |
HIV-1 Natural resistance HESN Vitamin D pathway Antiviral agents Epistasis Allelic heterogeneity Association study HIV-1 Natural resistance HESN Vitamin D pathway Antiviral agents Antiviral agents Epistasis Allelic heterogeneity Association study |
| dc.subject.other.spa.fl_str_mv |
HIV-1 Natural resistance HESN Vitamin D pathway Antiviral agents Antiviral agents Epistasis Allelic heterogeneity Association study |
| description |
Vitamin 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. |
| publishDate |
2019 |
| dc.date.accessioned.none.fl_str_mv |
2019-12-17T17:35:27Z |
| dc.date.available.none.fl_str_mv |
2019-12-17T17:35:27Z |
| dc.date.issued.none.fl_str_mv |
2019-05-16 |
| dc.type.none.fl_str_mv |
Artículo |
| dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
| dc.type.coarversion.none.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.version.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
http://purl.org/coar/resource_type/c_6501 |
| status_str |
publishedVersion |
| dc.identifier.issn.spa.fl_str_mv |
1567-1348 |
| dc.identifier.uri.spa.fl_str_mv |
10.1016/j.meegid.2019.05.014 |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/20.500.12494/15802 |
| dc.identifier.bibliographicCitation.spa.fl_str_mv |
Aguilar Jiménez W., Zapata W., Rivero Juárez A., Pineda J. A., Laplana M., Taborda N. A., Biasin M., Clerici M., Caruz A., Fibla J., Rugeles M. T. (2019) Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability. Infect Genet Evol. 2019 Sep;73:276-286. doi: 10.1016/j.meegid.2019.05.014. Recuperado de: |
| identifier_str_mv |
1567-1348 10.1016/j.meegid.2019.05.014 Aguilar Jiménez W., Zapata W., Rivero Juárez A., Pineda J. A., Laplana M., Taborda N. A., Biasin M., Clerici M., Caruz A., Fibla J., Rugeles M. T. (2019) Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability. Infect Genet Evol. 2019 Sep;73:276-286. doi: 10.1016/j.meegid.2019.05.014. Recuperado de: |
| url |
https://hdl.handle.net/20.500.12494/15802 |
| dc.relation.isversionof.spa.fl_str_mv |
https://www.sciencedirect.com/science/article/pii/S1567134819300929?via%3Dihub |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Infection, Genetics and Evolution |
| dc.relation.references.spa.fl_str_mv |
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Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1. Microbes Infect 18 (3), 211-219. doi:10.1016/j.micinf.2015.10.009. Zapata, W., Aguilar-Jimenez, W., Pineda-Trujillo, N., Rojas, W., Estrada, H., Rugeles, M.T., 2013. Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to HIV in serodiscordant couples from colombia. AIDS Res Hum Retroviruses 29 (12), 1594-1603. doi:10.1089/AID.2012.0299. Zapata, W., Rodriguez, B., Weber, J., Estrada, H., Quiñones-Mateu, M., Zimermman, P., . . . Rugeles, M., 2008. Increased Levels of Human Beta-Defensins mRNA in Sexually HIV-1 Exposed But Uninfected Individuals. Current HIV Research 6 (6), 531-538. |
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Zapata Builes, WildemanAguilar Jiménez, WbeimarRivero Juárez, AntonioPineda, Juan A.Laplana, MarinaTaborda, Natalia AndreaBiasin, MaraClerici, MarioCaruz, AntonioFibla, JoanRugeles López, María Teresa732019-12-17T17:35:27Z2019-12-17T17:35:27Z2019-05-161567-134810.1016/j.meegid.2019.05.014https://hdl.handle.net/20.500.12494/15802Aguilar Jiménez W., Zapata W., Rivero Juárez A., Pineda J. A., Laplana M., Taborda N. A., Biasin M., Clerici M., Caruz A., Fibla J., Rugeles M. T. (2019) Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability. Infect Genet Evol. 2019 Sep;73:276-286. doi: 10.1016/j.meegid.2019.05.014. Recuperado de:Vitamin 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.https://scienti.minciencias.gov.co/cvlac/EnProdArticulo/query.do?cod_producto=73&cod_rh=0000157775https://orcid.org/0000-0002-7351-8738COL0112548wildeman.zapatab@campusucc.edu.coaguilar.wb@gmail.commaria.rugeles@udea.edu.comara.biasin@unimi.itmario.clerici@unimi.itcaruz@ujaen.esjoan.fibla@cmb.udl.catarjvet@gmail.comnataliataborda@gmail.commarinalaplana@gmail.comjapineda@telefonica.nethttps://scholar.google.com.co/citations?hl=en&user=VLZxl1UAAAAJ10Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellin, ColombiaMedicinaMedellínhttps://www.sciencedirect.com/science/article/pii/S1567134819300929?via%3DihubInfection, Genetics and EvolutionAbboud, M., Puglisi, D.A., Davies, B.N., Rybchyn, M., Whitehead, N.P., Brock, K.E., . . . Mason, R.S., 2013. Evidence for a specific uptake and retention mechanism for 25- hydroxyvitamin D (25OHD) in skeletal muscle cells. Endocrinology 154 (9), 3022- 3030. doi:10.1210/en.2012-2245.Aguilar-Jimenez, W., Villegas-Ospina, S., Gonzalez, S., Zapata, W., Saulle, I., Garziano, M., . . . Rugeles, M.T., 2016a. Precursor forms of Vitamin D reduce HIV-1 infection in vitro. Journal of acquired immune deficiency syndromes 73 (5), 497-506. doi:10.1097/QAI.0000000000001150.Aguilar-Jiménez, W., Zapata, W., Caruz, A., Rugeles, M.T., 2013. High transcript levels of vitamin D receptor are correlated with higher mRNA expression of human beta defensins and IL-10 in mucosa of HIV-1-exposed seronegative individuals. PLoS One 8 (12), e82717. doi:10.1371/journal.pone.0082717.Aguilar-Jimenez, W., Zapata, W., Rugeles, M.T., 2013. Vitamin D involvement in the pathogenesis of human immunodeficiency virus type 1. 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Genetics and biology of vitamin D receptor polymorphisms. Gene 338 (2), 143-156.UNAIDS, 2017. 2017 GLOBAL HIV STATISTICSVillamor, E., 2006. A potential role for vitamin D on HIV infection? Nutrition reviews 64 (5 Pt 1), 226-233.Wang, T.T., Nestel, F.P., Bourdeau, V., Nagai, Y., Wang, Q., Liao, J., . . . White, J.H., 2004. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173 (5), 2909-2912.Wu, Y., Zhu, X., Chen, J., Zhang, X., 2013. EINVis: a visualization tool for analyzing and exploring genetic interactions in large-scale association studies. Genet Epidemiol 37 (7), 675-685. doi:10.1002/gepi.21754.Yin, J., Liu, H., Yi, X., Wu, W., Amos, C.I., Fang, S., . . . Wei, Q., 2016. Genetic variants in the vitamin D pathway genes VDBP and RXRA modulate cutaneous melanoma disease-specific survival. Pigment Cell Melanoma Res 29 (2), 176-185. doi:10.1111/pcmr.12437.Zapata, W., Aguilar-Jimenez, W., Feng, Z., Weinberg, A., Russo, A., Potenza, N., . . . Rugeles, M.T., 2016. Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1. Microbes Infect 18 (3), 211-219. doi:10.1016/j.micinf.2015.10.009.Zapata, W., Aguilar-Jimenez, W., Pineda-Trujillo, N., Rojas, W., Estrada, H., Rugeles, M.T., 2013. Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to HIV in serodiscordant couples from colombia. AIDS Res Hum Retroviruses 29 (12), 1594-1603. doi:10.1089/AID.2012.0299.Zapata, W., Rodriguez, B., Weber, J., Estrada, H., Quiñones-Mateu, M., Zimermman, P., . . . Rugeles, M., 2008. Increased Levels of Human Beta-Defensins mRNA in Sexually HIV-1 Exposed But Uninfected Individuals. Current HIV Research 6 (6), 531-538.HIV-1Natural resistanceHESNVitamin D pathwayAntiviral agentsEpistasisAllelic heterogeneityAssociation studyHIV-1Natural resistanceHESNVitamin D pathwayAntiviral agentsAntiviral agentsEpistasisAllelic heterogeneityAssociation studyGenetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variabilityArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribución – No comercial – Sin Derivarinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationORIGINALVitD Genetic Paper Corrected 1 Apr 2019Final.pdfVitD Genetic Paper Corrected 1 Apr 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