Association of Single Nucleotide Polymorphisms with Dyslipidemia in Antiretroviral Exposed HIV Patients in a Ghanaian population

Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year and 85 aged matched apparently healthy control subjects with no history of HIV and dyslipidemia. Fasting blood was collected into EDTA tube for lipids measurements. Lipid profiles were determined as a measure of dyslipidemia. HIV-infected patients were categorized into two groups; those with dyslipidemia(HIV-Dys+) (n=90; 31.1%) and without dyslipidemia (n=199; 68.9%) based on the NCEP-ATP III criteria. Four candidate single nucleotide polymorphisms (SNPs) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex Ligation Detection Reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), and rs10892151 (T/T) and rs662799 (G/G) among HIV+Dys+ subjects were 5.5%, 14.4%, 6.6% and 10.0%; 2.0% 9.1%, 6.5% and 4.0% among HIV+Dys- subjects while 3.5%, 4.7%, 4.7% and 2.4% were observed in HIV-Dys- subjects. Statistically significant difference in genotypic prevalence of APOA5 polymorphisms was observed among different groups (p=0.0196). Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR =4.01, 95%CI(1.57-22.39), p=0.004] were significantly more likely to develop dyslipidemia after controlling for age, gender, treatment duration and CD4 counts among the HIV+Dys+ subjects. There was also a significant associated between GG genotype of ABCA1 and dyslipidemia [aOR =3.29, 95% (1.08 −12.43); p=0.042]. Individuals with the rare homozygote variant (GG) of APOA5 (rs662799) were significantly associated with increased likelihood of developing dyslipidemia [OR =2.24, 95% CI (1.20 −6.83); p=0.0370] holding other variables constant in the HIV+Dys- subjects. Our data accentuate the presence of SNPs in four candidate genes and its association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population especially variants in APOA5-rs662799 ABCA1-rs2066714 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and its association with dyslipidemia.

Efavirenz-induced neurological symptoms in rare homozygote CYP2B6 *2/*2 (C64T)

Some of the HIV-1-infected patients who were given highly active anti-retroviral therapy (HAART) including efavirenz (EFV) presented adverse central nervous system (CNS) symptoms such as fatigue and insomnia. The incidence of adverse CNS symptoms is associated with hepatic cytochrome P450 isozymes (CYP2B6) polymorphisms. For example, CYP2B6 *6 (G516T and A785G) and *7 (G516T, A785G and C1459T) prolonged the EFV half-life despite discontinuation of EFV. CYP2B6 *2/*2 (C64T) is extremely rare and there have been no data describing the EFV plasma concentrations in C64T homozygous patients, who developed adverse CNS symptoms. C64T homozygous possibly has some catalytic defects.