SINGLE NUCLEOTIDE POLYMORPHISMS IN LCAT MAY CONTRIBUTE TO DYSLIPIDAEMIA IN HIV INFECTED INDIVIDUALS ON HAART IN AGHANAIAN POPULATION

Abstract

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 defned based on the NCEP-ATP III criteria. HIV-infected individuals on HAART with dyslipidaemia were classifed as cases while those without dyslipidaemia were grouped as controls. Lipid profle 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 signifcant SNPs were identifed in exons 1 and 4 for LCAT whereas 25 non-clinically signifcant SNPs were identifed 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 signifcantly associated with dyslipidaemic outcomes in the study population (p= 0.0004). A total of 25 SNPs were identifed in exons 5 and 6 of LPL; 22 were substitutions, and 3 were insertions. However, none of the 25 SNPs identifed in LPL exon 5 and 6 were statistically signifcant. SNPs in LCAT may independently contribute to dyslipidaemia among Ghanaian HIV-infected individuals on HAART, thus, allowing genetic and/or functional diferential diagnosis of dyslipidaemia and creating an opportunity for potentially preventive options.