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. 2019 Apr;7(4):e00598.
doi: 10.1002/mgg3.598. Epub 2019 Mar 12.

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

HariOm Singh  1 , Sonam Lata  1 , T N Dhole  2 , Raman R Gangakhedkar  3
Affiliations

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

HariOm Singh et al. Mol Genet Genomic Med. 2019 Apr.

Abstract

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.

Keywords: ARV-associated hepatotoxicity; CYP2B6; HIV patients; NNRTI drugs; genetic polymorphism.

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Conflict of interest statement

None declared.

References

    1. Bissell, D. M. , Gores, G. J. , Laskin, D. L. , & Hoofnagle, J. H. (2001). Drug‐induced liver injury: Mechanisms and test systems. Hepatology, 33(4), 1009–1013. 10.1053/jhep.2001.23505 - DOI - PubMed
    1. Cabrera, S. E. , Santos, D. , Valverde, M. P. , Domínguez‐Gil, A. , González, F. , Luna, G. , & García, M. J. (2009). Influence of the cytochrome P450 2B6 genotype on population pharmacokinetics of efavirenz in human immunodeficiency virus patients. Antimicrobial Agents and Chemotherapy, 53(7), 2791–2798. 10.1128/aac.01537-08 - DOI - PMC - PubMed
    1. Carr, D. F. , La Porte, C. J. , Pirmohamed, M. , Owen, A. , & Cortes, C. P. (2010). Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort. Journal of Antimicrobial Chemotherapy, 65(9), 1889–1893. 10.1093/jac/dkq260 - DOI - PMC - PubMed
    1. Chen, J. , Sun, J. , Ma, Q. , Yao, Y. , Wang, Z. , Zhang, L. , … Lu, H. (2010). CYP2B6 polymorphism and nonnucleoside reverse transcriptase inhibitor plasma concentrations in Chinese HIV‐infected patients. Therapeutic Drug Monitoring, 32(5), 573–578. 10.1097/FTD.0b013e3181ea953c - DOI - PubMed
    1. Cho, J. Y. , Lim, H. S. , Chung, J. Y. , Yu, K. S. , Kim, J. R. , Shin, S. G. , & Jang, I. J. (2004). Haplotype structure and allele frequencies of CYP2B6 in a Korean population. Drug Metabolism and Disposition, 32(12), 1341–1344. 10.1124/dmd.104.001107 - DOI - PubMed

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