Occurrence of DAT1 (VNTR) Polymorphism in Individuals with HIV infection

Abstract

Antiretroviral treatment (ART) have been reported to make changes in the functioning of dopaminergic neurons by altering the expression of dopamine active transporter (DAT). ART containing efavirenz drug have 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. To assess the polymorphism in the human gene DAT1 including variable number tandem repeats (VNTR) from individuals having an infection of HIV. 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. 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 having 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 increasing 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 had 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 have indicated a hazard for progression of HIV infection and increase in severity of hepatotoxicity (OR = 1.47, P = 0.85; OR = 1.73; P = 0.32). The genetic polymorphism with DAT19/10 genotype was linked with the progression of HIV infection and in the advancement of HIV-related illnesses.