IL18 gene polymorphism and its influence on CD4+ T-cell recovery in HIV-positive patients receiving antiretroviral therapy.
Infect Genet Evol
; 75: 103997, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31401307
ABSTRACT
BACKGROUND:
Pyroptosis has been reported to be critical in human immunodeficiency virus type 1 (HIV-1) pathogenesis and acquired immunodeficiency syndrome (AIDS) progression. Even after achieving viral suppression to undetectable levels during antiretroviral therapy (ART), exacerbated CD4+ T-cell death by pyroptosis has been suggested as one of the main causes of immunological non-response. Thus, variants in genes of pyroptosis pathway were studied in individuals with poor CD4+ T-cell reconstitution under antiretroviral therapy against HIV-1.METHODS:
248 virologically suppressed ART-treated patients, 126 immunological non-responders (INR) and 122 immunological responders (IR) were recruited. Genotyping was performed using TaqMan probe-based realtime PCR platform. Genotype-guided flow cytometry analysis with general and recent thymic emigrant (RTE) CD4+ T-cells in pyroptosis was performed based on associated polymorphisms.RESULTS:
Both IL18 rs187238 G allele and GG genotype were associated as protection factors against poor CD4+ T-cell recovery (ORâ¯=â¯0.22; 95%CIâ¯=â¯0.50-0.77; Pâ¯=â¯.010 and ORâ¯=â¯0.58; 95%CIâ¯=â¯0.36-0.93; Pâ¯=â¯.022, respectively). It was demonstrated a statistical association between IL18 rs187238 genotypes of ART-treated patients and death by Caspase-1 levels (Pâ¯=â¯.020). The GG genotype showed lower pyroptotic RTE CD4+ T-lymphocytes levels in the ART-treated groups comparing with CC (Pâ¯=â¯.029) and CG (Pâ¯=â¯.018) genotypes, suggesting that the G allele presence may be related to a lower IL-18 production and thus reduced dead CD4+ T-cells levels by Caspase-1.CONCLUSION:
We observed that IL18 G variant allele and genotype were associated with a better immunological response, which may influence on immunological recovery of HIV-positive patients receiving antiretroviral therapy, and low Caspase-1 activity levels was observed on GG genotype when compared CC genotypes.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Linfocitos T CD4-Positivos
/
Infecciones por VIH
/
Recuento de Linfocito CD4
/
Interleucina-18
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
Infect Genet Evol
Asunto de la revista:
BIOLOGIA
/
DOENCAS TRANSMISSIVEIS
/
GENETICA
Año:
2019
Tipo del documento:
Article