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CYP 1A1m1 and CYP 2C9*2 and *3 polymorphism and risk to develop ARV ‐associated hepatotoxicity and its severity
Author(s) -
Singh HariOm,
Lata Sonam,
Nema Vijay,
Samani Dharmesh,
Ghate Manisha,
Gangakhedkar Raman R.
Publication year - 2017
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12683
Subject(s) - genotype , nevirapine , genotyping , biology , pharmacology , cytochrome p450 , medicine , immunology , enzyme , gene , genetics , human immunodeficiency virus (hiv) , viral load , biochemistry , antiretroviral therapy
Non‐nucleoside reverse transcriptase inhibitors are metabolized in the liver by cytochrome P450 ( CYP ) isoenzymes. Variations in the genes encoding these enzymes may influence the activity of corresponding metabolizing enzymes. This study aimed at assessing association of CYP 2C9 *2 430C/T, CYP 2C9* 31075A/C, and CYP 1A1m1 3801T/C polymorphism with risk to develop ARV Antiretroviral‐associated hepatotoxicity and its severity. In this case–control study, genotyping of CYP 2C9 *2, CYP 2C9*3 , and CYP 1A1m1 genes was done in 34 HIV ‐infected individuals with hepatotoxicity and 131 without hepatotoxicity, and 153 unrelated healthy individuals using PCR ‐ RFLP . CYP 1A1m1 3801 CC genotype was likely to be associated with severe ARV ‐associated hepatotoxicity ( OR = 1.78, p = 0.70). CYP 1A1m1 3801 CC genotype and combined genotype TC + CC were likely to be associated with development of ARV ‐associated hepatotoxicity ( OR = 2.57, p = 0.08; OR = 1.42, p = 0.17). CYP 1A1m1 3801 CC genotype among advanced and intermediate HIV disease stage was likely to be associated with advancement of disease ( OR = 2.56, p = 0.77; OR = 2.37, p = 0.45). CYP 2C9 *31075 AC genotype among alcohol users was likely to be associated with development of ARV ‐associated hepatotoxicity ( OR = 1.67, p = 0.38). CYP 1A1m1 3801 TC genotype and combined genotype TC + CC among nevirapine users were likely to be associated with severe ARV ‐associated hepatotoxicity ( OR = 3.68, p = 0.27; OR = 4.91, p = 0.13). Among those who received nevirapine, presence of CYP 1A1m1 3801 TC genotype was likely to be associated with increased risk of development of ARV ‐associated hepatotoxicity ( OR = 1.50, p = 0.78). CYP 1A1m1 3801 TC , 3801 CC , and CYP 2C9*3 1075 AC genotypes among combined alcohol + nevirapine users increased the risk of development of ARV ‐associated hepatotoxicity ( OR = 1.41, p = 0.53; OR = 1.49, p = 0.83; OR = 1.78, p = 0.35). In conclusion, individuals with CYP 1A1m1 3801 CC and 3801 TC genotypes independently and in the presence of alcohol and nevirapine usage is likely to be associated with increased risk of development of ARV ‐associated hepatotoxicity, its severity, and advancement of disease. CYP 2C9*3 1075 AC genotype with combined alcohol and nevirapine usage indicated a risk for development of ARV ‐associated hepatotoxicity.