Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study

• Published in: PloS one Vol. 15; no. 1; p. e0227779
• Main Authors: Obirikorang, Christian, Acheampong, Emmanuel, Quaye, Lawrence, Yorke, Joseph, Amos-Abanyie, Ernestine Kubi, Akyaw, Priscilla Abena, Anto, Enoch Odame, Bani, Simon Bannison, Asamoah, Evans Adu, Batu, Emmanuella Nsenbah
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2020; Public Library of Science (PLoS)
• Subjects: ABCA1 protein; Adenosine triphosphate; Adult; Anti-Retroviral Agents - adverse effects; Anti-Retroviral Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Apolipoprotein A-V - genetics; Apolipoproteins; ATP-binding protein; Automation; Biology and Life Sciences; Blood pressure; Case-Control Studies; CD4 antigen; Cell adhesion & migration; Cholesterol; Correlation analysis; Deoxyribonucleic acid; DNA; Dyslipidemia; Dyslipidemias - blood; Dyslipidemias - chemically induced; Dyslipidemias - etiology; Dyslipidemias - genetics; Ethylenediaminetetraacetic acids; Female; Gene polymorphism; Genes; Genetic diversity; Genetic factors; Genetic Predisposition to Disease; Genetic variance; Genotyping; Ghana; Health sciences; HIV; HIV Infections - blood; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - genetics; Human immunodeficiency virus; Humans; Kidney diseases; Lipids; Lipoprotein (low density) receptors; Lipoproteins; Longitudinal studies; Male; Medical research; Medicine; Medicine and Health Sciences; Metabolic disorders; Metabolism; Middle Aged; Mutation; Nucleotides; Patients; People and Places; Polymorphism; Polymorphism, Single Nucleotide; Population; Population genetics; Population studies; Receptors, LDL - genetics; Single-nucleotide polymorphism; Statistical analysis; Studies; Triglycerides; Ghana; Australia; Africa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0227779

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.