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This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Accion Estrategica en Salud, Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (2013-2016) and cofinanced by Instituto de Salud Carlos III (Subdireccion General de Evaluacion) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigacion Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid B2017/BMD-3703. Programa de Investigacion de la Consejeria de Sanidad de la Comunidad de Madrid to JLJ. CIBER-BBN is an initiative funded by the VI National R& D& i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. COST CA17140 Cancer Nanomedicine-Front the Bench to Bebside. AFR are supported and funded by Instituto de Salud Carlos III [grant number CP14/0010].

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VDR rs2228570 Polymorphism Is Related to Non-Progression to AIDS in Antiretroviral Therapy Naive HIV-Infected Patients

Publicated to:Journal Of Clinical Medicine. 8 (3): 311- - 2019-03-05 8(3), DOI: 10.3390/jcm8030311

Authors: Jimenez-Sousa, Maria A; Luis Jimenez, Jose; Fernandez-Rodriguez, Amanda; Brochado-Kith, Oscar; Maria Bellon, Jose; Diez, Cristina; Bernal-Morell, Enrique; Viciana, Pompeyo; Munoz-Fernandez, Maria A; Resino, Salvador; Moreno, Santiago; Dalmau, David; Garcia, Federico; Vidal, Francesc; Angeles Munoz-Fernandez, M; Maria Garcia-Merino, Isabel; Consuegra Fernandez, Irene; Gomez Rico, Coral; Gallego de la Fuente, Jorge; Palau Concejo, Paula; Portilla, Joaquin; Merino, Esperanza; Reus, Sergio; Boix, Vicente; Giner, Livia; Gadea, Carmen; Portilla, Irene; Pampliega, Maria; Diez, Marcos; Carlos Rodriguez, Juan; Sanchez-Paya, Jose; Luis Gomez, Juan; Hernandez, Jehovana; Remedios Aleman, Maria; del Mar Alonso, Maria; Inmaculada Hernandez, Maria; Diaz-Flores, Felicitas; Garcia, Dacil; Pelazas, Ricardo; Lopez Lirola, Ana; Sanz Moreno, Jose; Arranz Caso, Alberto; Hernandez Gutierrez, Cristina; Novella Mena, Maria; Rubio, Rafael; Pulido, Federico; Bisbal, Otilia; Hernando, Asuncion; Dominguez, Lourdes; Rial Crestelo, David; Bermejo, Laura; Santacreu, Mireia; Antonio Iribarren, Jose; Arrizabalaga, Julio; Jose Aramburu, Maria; Camino, Xabier; Rodriguez-Arrondo, Francisco; Angel von Wichmann, Miguel; Pascual Tome, Lidia; Angel Goenaga, Miguel; Jesus Bustinduy, Ma; Azkune, Harkaitz; Ibarguren, Maialen; Lizardi, Aitziber; Kortajarena, Xabier; Gutierrez, Felix; Masia, Mar; Padilla, Sergio; Navarro, Andres; Montolio, Fernando; Robledano, Catalina; Gregori Colome, Joan; Adsuar, Araceli; Pascual, Rafael; Fernandez, Marta; Garcia, Elena; Alberto Garcia, Jose; Barber, Xavier; Berenguer, Juan; Bernaldo de Quiros, Juan Carlos Lopez; Gutierrez, Isabel; Ramirez, Margarita; Padilla, Belen; Gijon, Paloma; Aldamiz-Echevarria, Teresa; Tejerina, Francisco; Jose Parras, Francisco; Balsalobre, Pascual; Perez Latorre, Leire; Peraire, Joaquin; Vilades, Consuelo; Veloso, Sergio; Vargas, Montserrat; Lopez-Dupla, Miguel; Olona, Montserrat; Rull, Anna; Rodriguez-Gallego, Esther; Alba, Veronica; Montero Alonso, Marta; Lopez Aldeguer, Jose; Blanes Julia, Marino; Tasias Pitarch, Maria; Castro Hernandez, Ivan; Calabuig Munoz, Eva; Cuellar Tovar, Sandra; Salavert Lleti, Miguel; Fernandez Navarro, Juan; Gonzalez-garcia, Juan; Arnalich, Francisco; Ramon Arribas, Jose; Bernardino de la Serna, Jose Ignacio; Miguel Castro, Juan; Escosa, Luis; Herranz, Pedro; Hontanon, Victor; Garcia-Bujalance, Silvia; Garcia Lopez-Hortelano, Milagros; Gonzalez-Baeza, Alicia; Luz Martin-Carbonero, Maria; Mayoral, Mario; Jose Mellado, Maria; Esteban Mican, Rafael; Montejano, Rocio; Luisa Montes, Maria; Moreno, Victoria; Perez-Valero, Ignacio; Rodes, Berta; Sainz, Talia; Sendagorta, Elena; Stella Alcariz, Natalia; Valencia, Eulalia; Ramon Blanco, Jose; Antonio Oteo, Jose; Ibarra, Valvanera; Metola, Luis; Sanz, Mercedes; Perez-Martinez, Laura; Jaen, Angels; Sanmarti, Montse; Cairo, Mireia; Martinez-Lacasa, Javier; Velli, Pablo; Font, Roser; Xercavins, Mariona; Alonso, Noemi; Rivero, Maria; Reparaz, Jesus; Ruiz de Alda, Maria Gracia; de Leon Cano, Maria Teresa; Ruiz de Galarreta, Beatriz Pierola; Segura, Ferran; Jose Amengual, Maria; Navarro, Gemma; Sala, Montserrat; Cervantes, Manuel; Pineda, Valentin; Calzado, Sonia; Navarro, Marta; de los Santos, Ignacio; Sanz Sanz, Jesus; Salas Aparicio, Ana; Sarria Cepeda, Cristina; Garcia-Fraile Fraile, Lucio; Martin Gayo, Enrique; Luis Casado, Jose; Dronda, Fernando; Moreno, Ana; Perez Elias, Maria Jesus; Gomez Ayerbe, Cristina; Gutierrez, Carolina; Madrid, Nadia; del Campo Terron, Santos; Marti, Paloma; Ansa, Uxua; Serrano, Sergio; Jesus Vivancos, Maria; Bernal, Enrique; Cano, Alfredo; Alcaraz Garcia, Antonia; Bravo Urbieta, Joaquin; Munoz, Angeles; Jose Alcaraz, Maria; del Carmen Villalba, Maria; Hernandez, Jose; Pena, Alejandro; Munoz, Leopoldo; Casas, Paz; Alvarez, Marta; Chueca, Natalia; Vinuesa, David; Martinez-Montes, Clara; Del Romero, Jorge; Rodriguez, Carmen; Puerta, Teresa; Carlos Carrio, Juan; Vera, Mar; Ballesteros, Juan; Ayerdi, Oskar; Riera, Melchor; Penaranda, Maria; Leyes, Maria; Angels Ribas, Ma; Campins, Antoni A; Vidal, Carmen; Fanjul, Francisco; Murillas, Javier; Homar, Francisco; Santos, Jesus; Gomez Ayerbe, Crisitina; Viciana, Isabel; Palacios, Rosario; Maria Gonzalez, Carmen; Espinosa, Nuria; Fernando Lopez-Cortes, Luis; Podzamczer, Daniel; Ferrer, Elena; Imaz, Arkaitz; Tiraboschi, Juan; Silva, Ana; Saumoy, Maria; Olalla, Julian; del Arco, Alfonso; de la Torre, Javier; Luis Prada, Jose; de Lomas Guerrero, Jose Maria Garcia; Perez Stachowski, Javier; Juan Martinez, Onofre; Jesus Vera, Francisco; Martinez, Lorena; Garcia, Josefina; Alcaraz, Begona; Jimeno, Amaya; Castro Iglesias, Angeles; Pernas Souto, Berta; Mena de Cea, Alvaro; Galera, Carlos; Albendin, Helena; Perez, Aurora; Iborra, Asuncion; Moreno, Antonio; Angustias Merlos, Maria; Vidal, Asuncion; Suarez-Garcia, Ines; Malmierca, Eduardo; Gonzalez-Ruano, Patricia; Martin Rodrigo, Dolores; Omar Mohamed-Balghata, Mohamed; Gomez Vidal, Maria Amparo; Estrada Perez, Vicente; Tellez Molina, Maria Jesus; Vergas Garcia, Jorge; Perez-Somarriba Moreno, Juncal; Gorgolas, Miguel; Cabello, Alfonso; Alvarez, Beatriz; Prieto, Laura; Galindo Puerto, Maria Jose; Fernando Vilalta, Ramon; Ferrer Ribera, Ana; Rivero Roman, Antonio; Brieva Herrero, Maria Teresa; Rivero Juarez, Antonio; Lopez Lopez, Pedro; Machuca Sanchez, Isabel; Pena Martinez, Jose; Cervero Jimenez, Miguel; Torres Perea, Rafael; Jusdado Ruiz-Capillas, Juan Jose; Pineda, Juan A

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Abstract

Background: Vitamin D is a fundamental regulator of host defenses by activating genes related to innate and adaptive immunity. In this study, we analyzed the association among single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, with clinical patterns of AIDS progression in antiretroviral treatment (ART)-naive HIV-infected patients. Methods: We conducted a retrospective study in 667 HIV-infected patients, who were classified within three groups according to their AIDS progression pattern (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)). Five VDR SNPs (rs11568820, rs4516035, rs2228570, rs1544410, and rs7975232) were genotyped using Agena Bioscience's MassARRAY platform. Results: Significant association results were found for rs2228570. Within all HIV patients, the presence of T allele at VDR rs2228570 SNP was protective against AIDS progression (ordinal outcome) under additive (adjusted odds ratio (aOR) = 0.75; p = 0.009), dominant (aOR = 0.69; p = 0.015), and codominant (aOR = 0.56; p = 0.017) inheritance models. In addition, the same allele was protective under additive and codominant inheritance models when we compared with LTNPs vs. RPs [aOR = 0.64 (p = 0.019) and aOR = 0.37 (p = 0.018), respectively] and when we compared MPs vs. RPs [aOR = 0.72 (p = 0.035) and aOR = 0.45 (p = 0.028), respectively]. Conclusions: The VDR rs2228570 T allele was related to a lower AIDS progression pattern in ART-naive HIV-infected patients. These findings expand upon the knowledge about HIV pathogenesis in untreated HIV-infected patients with different clinical outcomes.

Keywords