Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression


Por: Restrepo C, Gutierrez-Rivas M, Pacheco YM, García M, Blanco J, Medrano LM, Navarrete-Muñoz MA, Gutiérrez F, Miralles P, Dalmau D, Gómez JL, Górgolas M, Cabello A, Resino S, Benito JM and Rallón N

Publicada: 28 mar 2019
Categoría: Multidisciplinary

Resumen:
Objective We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts. Methods A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count <200 cells/mu L and successful viral control for two years. CD4 count increase below 200 cells/mu L after two years on cART was used to define INR (immunological nonresponder) patients. Polymorphisms in CXCL12, CCL5 and CCR2 genes were genotyped using sequenom's MassARRAY platform. Results Thirty two percent (134/412) of patients were classified as INR. After adjusting by age, route of HIV infection, length of infection before cART and viral hepatitis coinfection, CCR2 rs1799864-AG genotype was significantly associated with INR status (OR [95% CI]: 1.80 [1.04-3.11]; p = 0.04), and CXCL1 2 rs1801157-TT genotype showed a trend (OR [95% CI]: 2.47 [0.96-6.35]; p = 0.06). Conclusions CCR2 rs1799864-AG or CXCL12 rs1801157-TT genotypes influence on the probability of poor CD4 recovery in the population of HIV patients starting cART with low CD4 counts. Genotyping of these polymorphisms could be used to estimate the risk of poor CD4 restoration, mainly in patients who are diagnosed late in the course of infection.

Filiaciones:
Restrepo C:
 HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain

 Hospital Universitario Rey Juan Carlos, Móstoles (Madrid), Spain

Gutierrez-Rivas M:
 Instituto de Salud Carlos III, Madrid, Spain

Pacheco YM:
 Laboratory of Immunology, Instituto de Biomedicina de Sevilla (IBiS)/UGC Clinical Laboratories, Hospital Universitario Virgen del Rocío, Sevilla, Spain

García M:
 HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain

 Hospital Universitario Rey Juan Carlos, Móstoles (Madrid), Spain

Blanco J:
 IrsiCaixa AIDS Research Institute, Badalona, Spain

Medrano LM:
 Instituto de Salud Carlos III, Madrid, Spain

Navarrete-Muñoz MA:
 HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain

 Hospital Universitario Rey Juan Carlos, Móstoles (Madrid), Spain

:
 Hospital General Universitario de Elche & University Miguel Hernández, Alicante, Spain

Miralles P:
 Hospital General Universitario Gregorio Marañón, Madrid, Spain

Dalmau D:
 Hospital Universitari Mutua Terrasa, Terrasa, Spain

Gómez JL:
 Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain

Górgolas M:
 Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

Cabello A:
 Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

Resino S:
 Instituto de Salud Carlos III, Madrid, Spain

Benito JM:
 HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain

 Hospital Universitario Rey Juan Carlos, Móstoles (Madrid), Spain

Rallón N:
 HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain

 Hospital Universitario Rey Juan Carlos, Móstoles (Madrid), Spain
ISSN: 19326203





PLoS One
Editorial
PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 14 Número: 3
Páginas:
WOS Id: 000462594000067
ID de PubMed: 30921390
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