Single nucleotide polymorphisms in LCAT may contribute to dyslipidaemia in HIV-infected individuals on HAART in a Ghanaian population

Autor: Moses Banyeh, Emmanuel Acheampong, Simon Bannison Bani, Christian Obirikorang, Yussif Adams, William K. B. A. Owiredu, Kwabena Owusu Danquah, Enoch Odame Anto, Peter Paul Mwinsanga Dapare, Lawrence Quaye, E. M. Der, Samuel Asamoah Sakyi
Rok vydání: 2020
Předmět:
0301 basic medicine
lcsh:Medicine
HIV Infections
Ghana
Polymerase Chain Reaction
Phosphatidylcholine-Sterol O-Acyltransferase
chemistry.chemical_compound
0302 clinical medicine
Polymorphism (computer science)
DNA sequencing
030212 general & internal medicine
lcsh:Science
education.field_of_study
Lipoprotein lipase
Multidisciplinary
medicine.diagnostic_test
Exons
Middle Aged
Cholesterol
Population study
lipids (amino acids
peptides
and proteins)
Adult
medicine.medical_specialty
Adolescent
Population
Genetic predisposition to disease
Single-nucleotide polymorphism
Polymorphism
Single Nucleotide
Article
Young Adult
03 medical and health sciences
Internal medicine
medicine
Humans
education
Triglycerides
Dyslipidemias
lcsh:R
Cholesterol
HDL
Case-control study
nutritional and metabolic diseases
Cholesterol
LDL
Sequence Analysis
DNA
030104 developmental biology
Endocrinology
chemistry
Case-Control Studies
lcsh:Q
Lipid profile
Zdroj: Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
ISSN: 2045-2322
DOI: 10.1038/s41598-020-76113-2
Popis: Highly active antiretroviral therapy (HAART) is known to cause lipid abnormalities such as dyslipidaemia in HIV-infected individuals. Yet, dyslipidaemia may not independently occur as it may be worsened by single nucleotide polymorphisms (SNPs) in lecithin cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). This case–control study was conducted in three-selected hospitals in the Northern part of Ghana. The study constituted a total of 118 HIV-infected participants aged 19–71 years, who had been on HAART for 6–24 months. Dyslipidaemia was defined based on the NCEP-ATP III criteria. HIV-infected individuals on HAART with dyslipidaemia were classified as cases while those without dyslipidaemia were grouped as controls. Lipid profile was measured using an automatic clinical chemistry analyzer and genomic DNA was extracted for PCR (GeneAmp PCR System 2700). Overall, the prevalence of dyslipidaemia was 39.0% (46/118). High levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and reduced levels of high-density lipoprotein cholesterol (HDL-C) were observed in all cases. A total of 256 selected PCR amplicons comprising 137 LPL (exons 3, 5 and 6) and 119 LCAT (exons 1, 4, and 6) were sequenced in 46 samples (Inqaba Biotech). Six (6) clinically significant SNPs were identified in exons 1 and 4 for LCAT whereas 25 non-clinically significant SNPs were identified for LPL in exons 5 and 6. At position 97 for LCAT exon 1, there was a deletion of the nucleotide, ‘A’ in 32.5% (13/40) of the sampled population while 67.5% (27/40) of the sample population retained the nucleotide, ‘A’ which was significantly associated with dyslipidaemic outcomes in the study population (p = 0.0004). A total of 25 SNPs were identified in exons 5 and 6 of LPL; 22 were substitutions, and 3 were insertions. However, none of the 25 SNPs identified in LPL exon 5 and 6 were statistically significant. SNPs in LCAT may independently contribute to dyslipidaemia among Ghanaian HIV-infected individuals on HAART, thus, allowing genetic and/or functional differential diagnosis of dyslipidaemia and creating an opportunity for potentially preventive options.
Databáze: OpenAIRE
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