HariOm Singh* and Sonam Lata Pages 8 - 17 ( 10 )
Background: Antiretroviral treatment (ART) has been reported to make changes in the functioning of dopaminergic neurons by altering the expression of dopamine active transporter (DAT). ART containing efavirenz drug has been related to show the adverse reactions on the central nervous system (CNS). Reported literature indicates the correlation of DAT19/10 genotype with the risk of progression of human immunodeficiency virus (HIV) infection.
Objective: The aim of this study was to assess the polymorphism in the human gene DAT1, including variable number tandem repeats (VNTR) from individuals having an infection of HIV.
Methods: Genotyping was completed by performing a polymerase chain reaction (PCR) in a total of 165 HIV-positive patients on ART treatment (34 were HIV-infected patients with hepatotoxicity, 131 HIV-infected patients) and 160 healthy controls without HIV infection.
Results: Incidence of DAT19/9, 8/9 genotypes, and allele with 9 repeats were higher in individuals having hepatotoxicity compared to those who do not have hepatotoxicity (5.9 vs. 0.8%, OR = 7.73; 2.9 vs. 0.8%, OR = 3.86; 20.58% vs. 14.12%, OR = 1.56). DAT19/10 genotype was related to severity of hepatotoxicity (OR = 1.86; P = 0.05). Upon comparison of genotype between individuals who do not have hepatotoxicity but had HIV infection and healthy controls without HIV infection, the dispersion of DAT1 10/11, 6/10 genotypes were greater in individuals with HIV infection (1.5% vs. 0.6%, OR = 2.73; 3.1% vs. 1.3%, OR = 2.73). DAT19/10 genotype was related to the people of advanced stage of HIV infection (OR = 2.05, P = 0.04). A higher incidence of DAT19/10 genotype was found in individuals with early stage of HIV infection than healthy controls (26.3 vs. 15.6%, OR = 1.93). In alcohol and tobacco consuming individuals with HIV infection and hepatotoxicity, DAT19/10 genotype has demonstrated hazard in the progression of HIV infection and an increased severity of hepatotoxic condition (OR = 1.40, P = 0.91, OR = 1.50; P = 0.91 and OR = 1.57, P = 0.39; OR = 2.70; P = 0.53). In patients with hepatotoxicity, nevirapine utilization with DAT19/10 genotype demonstrated an increase in severity of hepatotoxicity (OR = 4.00, P = 0.41). In individuals with HIV infection and hepatotoxicity, alcohol and nevirapine usage, along with DAT1 9/10 genotype, indicated a risk for progression of HIV infection and severity of hepatotoxicity (OR = 1.47, P = 0.85; OR = 1.73; P = 0.32).
Conclusion: The genetic polymorphism with DAT19/10 genotype was linked with the progression of HIV infection and in the advancement of HIV-related illnesses.
HIV, ART-related hepatotoxicity, genetic polymorphism, dopamine active transporter, efavirenz, progression of HIV infection.
Department of Molecular Biology, National AIDS Research Institute, Pune 411026, Department of Molecular Biology, National AIDS Research Institute, Pune 411026