Prevalence ofCYP2D6*4 1934G/A polymorphism in Western IndianHIVpatients

Abstract

Hepatic CYP2D6 enzyme metabolizes antiretroviral drugs (ARVs) including nevirapine. Polymorphism in CYP2D6 gene affects drug metabolism and displays distinctive phenotypes in the population. Hence, we investigated the prevalence of CYP2D6*4 1934G/A polymorphism in a total of 165 HIV patients that include 34 with and 131 without hepatotoxicity and 160 unrelated healthy controls by the PCR‐RFLP method. The prevalence of CYP2D6*4 1934AA genotype was higher in total HIV patients as compared to healthy controls (1.81% vs 0.6%, OR = 2.86). Similarly, CYP2D6*4 1934AA genotype was much more prevalent in HIV patients without hepatotoxicity as compared to healthy controls (2.3% vs 0.6%, OR = 2.87). Likewise, CYP2D6*4 1934AA genotype was predominant in advanced HIV disease stage as compared to healthy controls (3.8% vs 0.6%, OR = 6.15). CYP2D6*4 1934GA genotype was distributed higher in HIV patients taking tobacco and nevirapine as compared to non‐users (23.3% vs 19.3%, OR = 1.21, 21.0% vs 16.7%, OR = 1.2). Likewise, CYP2D6*4 1934GA genotype was overrepresented in patients with hepatotoxicity taking alcohol + nevirapine as compared to alcohol non‐users + nevirapine users (20.00% vs 16.67%, OR = 1.25). Thus, there was no significant difference in genotype or allele frequencies of CYP2D6*4 1934G/A polymorphism between the patients with hepatotoxicity and those without or healthy controls.

Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19

“…We included studies with a small number of participants ( n ≥ 20), as well as controls from case–control studies, which increased the number of studies we could include. Bias was minimized by excluding studies of populations diagnosed with a disease to prevent confounding our data (i.e., disease associations with specific allele frequencies 88 – 94 ). On the other hand, some large studies had to be excluded due to their inclusion of non-healthy individuals, which might have biased the outcomes of some countries 95 .…”

Cyp2d6 Expression Is Cumulatively Up Regulated in Multidrug Treated Hepatoma Cells: A Predective Pharmacogenetics in Vitro Model

“…Also, CYPs play an important role in carcinogens and anti-cancer drug biotransformation. Among CYPs, Debrisoquine 4-Hydroxylayase (CYP2D6) has special importance, where it was introduced as a predictor of drug related responsiveness, inter-individual variation in addition to the relation between its polymorphism and the development of cancers and other pathological condition (Bezerra et al, 2018;Singh et al, 2018). These observations relay on some unique features of CYP2D6 including its high genetic polymorphism (Zhou, 2009).…”