Cargando…

Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity

BACKGROUND: Hepatic enzyme cytochrome P450 2B6 (CYP2B6) plays a role in the metabolism of efavirenz drugs. CYP2B6 516G>T variation showed an implication for HIV treatment. METHODS: CYP2B6 516G>T polymorphism was genotyped in a total 165 HIV patients that include 34 with and 131 without hepatot...

Descripción completa

Detalles Bibliográficos
Autores principales: Singh, HariOm, Lata, Sonam, Dhole, T. N., Gangakhedkar, Raman R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465650/
https://www.ncbi.nlm.nih.gov/pubmed/30864294
http://dx.doi.org/10.1002/mgg3.598
_version_ 1783410971811774464
author Singh, HariOm
Lata, Sonam
Dhole, T. N.
Gangakhedkar, Raman R.
author_facet Singh, HariOm
Lata, Sonam
Dhole, T. N.
Gangakhedkar, Raman R.
author_sort Singh, HariOm
collection PubMed
description BACKGROUND: Hepatic enzyme cytochrome P450 2B6 (CYP2B6) plays a role in the metabolism of efavirenz drugs. CYP2B6 516G>T variation showed an implication for HIV treatment. METHODS: CYP2B6 516G>T polymorphism was genotyped in a total 165 HIV patients that include 34 with and 131 without hepatotoxicity and 155 healthy individuals by the PCR‐RFLP. RESULTS: In patients with hepatotoxicity, the prevalence of CYP2B6 516TT genotype was higher as compared to healthy individuals (35.3% vs. 30.5%, OR = 1.74). Patients with hepatotoxicity using tobacco had a higher prevalence of genotypes CYP2B6 516GT, 516TT, 516GT+TT as compared to healthy individuals (28.57% vs. 25.93%; 57.14% vs. 29.63%; 85.71% vs. 55.56%). Likewise, hepatotoxicity in patients consuming alcohol showed higher distributions of CYP2B6 516GT, 516TT, 516GT+TT genotypes (57% vs. 25.93%; 42.86% vs. 33.33%; 71.43% vs. 59.26%). Nevirapine users with hepatotoxicity overrepresented genotypes CYP2B6 TT and 516GT+TT as compared to efavirenz users (47.83% vs. 45.45%, OR = 6.88, 65.22% vs. 54.55%, OR = 1.56). Similarly, in nevirapine +alcohol users with hepatotoxicity, the frequency of CYP2B6 516GT, 516GT+TT genotypes was higher than with nevirapine +alcohol nonusers (40.0% vs. 11.11%, OR = 8.00, 80.0% vs. 27.78%, OR = 4.00). In HIV patients, nevirapine users had higher frequency of CYP2B6 516GT, 516GT+TT genotypes as compared to efavirenz users (42.02% vs. 25.00%, OR = 2.53; 72.27% vs. 58.33%, OR = 1.86). Likewise, in HIV patients, genotypes CYP2B6 516GT, 516GT+TT were predominant with nevirapine +alcohol users as compared to nevirapine +alcohol nonusers (57.89% vs. 34.57%, OR = 2.46; 78.95% vs. 69.14%, OR = 1.67). In multivariate logistic regression, taking nevirapine had a protection for severity of ARV‐associated hepatotoxicity (OR = 0.23, p = 0.005). CONCLUSIONS: No significant association was detected between CYP2B6 516G>T polymorphism and susceptibility to ARV‐associated hepatotoxicity.
format Online
Article
Text
id pubmed-6465650
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-64656502019-04-23 Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity Singh, HariOm Lata, Sonam Dhole, T. N. Gangakhedkar, Raman R. Mol Genet Genomic Med Original Articles BACKGROUND: Hepatic enzyme cytochrome P450 2B6 (CYP2B6) plays a role in the metabolism of efavirenz drugs. CYP2B6 516G>T variation showed an implication for HIV treatment. METHODS: CYP2B6 516G>T polymorphism was genotyped in a total 165 HIV patients that include 34 with and 131 without hepatotoxicity and 155 healthy individuals by the PCR‐RFLP. RESULTS: In patients with hepatotoxicity, the prevalence of CYP2B6 516TT genotype was higher as compared to healthy individuals (35.3% vs. 30.5%, OR = 1.74). Patients with hepatotoxicity using tobacco had a higher prevalence of genotypes CYP2B6 516GT, 516TT, 516GT+TT as compared to healthy individuals (28.57% vs. 25.93%; 57.14% vs. 29.63%; 85.71% vs. 55.56%). Likewise, hepatotoxicity in patients consuming alcohol showed higher distributions of CYP2B6 516GT, 516TT, 516GT+TT genotypes (57% vs. 25.93%; 42.86% vs. 33.33%; 71.43% vs. 59.26%). Nevirapine users with hepatotoxicity overrepresented genotypes CYP2B6 TT and 516GT+TT as compared to efavirenz users (47.83% vs. 45.45%, OR = 6.88, 65.22% vs. 54.55%, OR = 1.56). Similarly, in nevirapine +alcohol users with hepatotoxicity, the frequency of CYP2B6 516GT, 516GT+TT genotypes was higher than with nevirapine +alcohol nonusers (40.0% vs. 11.11%, OR = 8.00, 80.0% vs. 27.78%, OR = 4.00). In HIV patients, nevirapine users had higher frequency of CYP2B6 516GT, 516GT+TT genotypes as compared to efavirenz users (42.02% vs. 25.00%, OR = 2.53; 72.27% vs. 58.33%, OR = 1.86). Likewise, in HIV patients, genotypes CYP2B6 516GT, 516GT+TT were predominant with nevirapine +alcohol users as compared to nevirapine +alcohol nonusers (57.89% vs. 34.57%, OR = 2.46; 78.95% vs. 69.14%, OR = 1.67). In multivariate logistic regression, taking nevirapine had a protection for severity of ARV‐associated hepatotoxicity (OR = 0.23, p = 0.005). CONCLUSIONS: No significant association was detected between CYP2B6 516G>T polymorphism and susceptibility to ARV‐associated hepatotoxicity. John Wiley and Sons Inc. 2019-03-12 /pmc/articles/PMC6465650/ /pubmed/30864294 http://dx.doi.org/10.1002/mgg3.598 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Singh, HariOm
Lata, Sonam
Dhole, T. N.
Gangakhedkar, Raman R.
Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity
title Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity
title_full Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity
title_fullStr Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity
title_full_unstemmed Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity
title_short Occurrence of CYP2B6 516G>T polymorphism in patients with ARV‐associated hepatotoxicity
title_sort occurrence of cyp2b6 516g>t polymorphism in patients with arv‐associated hepatotoxicity
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465650/
https://www.ncbi.nlm.nih.gov/pubmed/30864294
http://dx.doi.org/10.1002/mgg3.598
work_keys_str_mv AT singhhariom occurrenceofcyp2b6516gtpolymorphisminpatientswitharvassociatedhepatotoxicity
AT latasonam occurrenceofcyp2b6516gtpolymorphisminpatientswitharvassociatedhepatotoxicity
AT dholetn occurrenceofcyp2b6516gtpolymorphisminpatientswitharvassociatedhepatotoxicity
AT gangakhedkarramanr occurrenceofcyp2b6516gtpolymorphisminpatientswitharvassociatedhepatotoxicity