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


Autoři: Christian Obirikorang aff001;  Emmanuel Acheampong aff001;  Lawrence Quaye aff003;  Joseph Yorke aff004;  Ernestine Kubi Amos-Abanyie aff005;  Priscilla Abena Akyaw aff005;  Enoch Odame Anto aff001;  Simon Bannison Bani aff003;  Evans Adu Asamoah aff001;  Emmanuella Nsenbah Batu aff001
Působiště autorů: Department of Molecular Medicine, School of Medical Science, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana aff001;  School of Medical and Health Science, Edith Cowan University, Joondalup, Australia aff002;  School of Allied Health Sciences, University of Development Studies, Tamale, Ghana aff003;  Department of Surgery, Komfo Anokye Teaching Hospital, Kumasi, Ghana aff004;  H3Africa Kidney Disease Research Project, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227779

Souhrn

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.

Klíčová slova:

Antiretroviral therapy – Dyslipidemia – Ghana – HIV – Cholesterol – Lipids – Lipoproteins – Variant genotypes


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