Abstract
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. Fasting blood was collected into EDTA tube for lipids measurement. Lipid profiles were used to define dyslipidemia based on the NCEP-ATP III criteria. HIV-infected subjects were categorized into two groups; those with dyslipidemia (cases) (n = 90; 31.1%) and without dyslipidemia (controls)(n = 199; 68.9%). Four candidate single nucleotide polymorphism (SNP) 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), rs10892151 (T/T) and rs662799 (G/G) among case subjects were 5.5%, 14.4%, 6.6% and 10.0% whiles 2.0% 9.1%, 6.5% and 4.0% were observed among control subjects. There were statistically significant differences in the genotypic prevalence of APOA5 (p = 0.0357) and LDLR polymorphisms (p = 0.0387) between case and control subjects. Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR = 2.38, 95%CI(1.06-6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia after controlling for age, gender, treatment duration, CD4 counts and BMI. Moreover, individuals with the rare homozygous genotype of ABCA1 (G/G) [aOR = 10.7(1.3-88.7), p = 0.0280] and LDLR (rs6511720) G>T [aOR = 61.2(7.6-493.4), p<0.0001) were more likely to have high levels of total cholesterol levels. Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799 and LDLR rs6511720 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 their associations with dyslipidemia.
Highlights
Global estimates report 37 million people living with Human Immunodeficiency Virus (HIV), out of which about 26 million reside in Sub-Saharan (SSA) [1]
Their association with dyslipidemia among HIV patients exposed to antiretroviral therapy (ART) in the Ghanaian population, especially variants in Apolipoprotein A5 (APOA5)-rs662799 and Low-density lipoprotein receptor (LDLR) rs6511720 respectively
These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients
Summary
Global estimates report 37 million people living with Human Immunodeficiency Virus (HIV), out of which about 26 million reside in Sub-Saharan (SSA) [1]. The prevalence of dyslipidemia is reportedly higher in people living with HIV due to the effect of ART in Ghana [9,10,11]. Lipid abnormalities have been reported to be frequently associated with HIV-infected individuals receiving protease inhibitors (PIs) and treatment-naïve HIV-infected patients, suggesting that HIV infection itself has a metabolic deleterious effect. Such reported side effects are not universal to all individuals on ART and may even vary in individuals with comparable ART, demographic, immunologic and virological characteristics [12,13,14]. High HDL cholesterol and apolipoprotein A-I (APOA-I) have been directly associated with a better immunological outcome [16]
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