Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study
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Date
2020-01-20
Journal Title
Journal ISSN
Volume Title
Publisher
Plos One
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.
Description
Research Article
Keywords
HIV patients, antiretroviral therapy (ART), single nucleotide polymorphism (SNP), polymorphisms