Prevalence of pathogenic genetic variants associated with familial hypercholesterolemia in Ghanaian children

Familial hypercholesterolemia (FH) is an important contributor to atherosclerotic cardiovascular disease (ASCVD) burden globally. FH disrupts cholesterol metabolism and causes lifelong elevation in low-density lipoprotein cholesterol (LDL-C). In sub-Saharan Africa (SSA), the increasing burden of ASCVD may be partly driven by genetic dyslipidemias of which FH is the commonest. However, there is absence of data on FH prevalence in SSA which delineates an important gap in the management of ASCVD. This study is the first to investigate the prevalence of pathogenic variants associated with FH in Ghana. We used 96 deidentified archived dried blood spot samples collected from a Ghanaian cohort, to determine the prevalence of pathogenic genetic variants associated with FH. These samples were collected from children under 9 years old as part of surveillance for antimalarial drug resistance in 2021. We searched the NCBI's ClinVar database and used in silico tools to identify 500–800 nucleotide base pair regions of interest in 3 genes known to harbor the commonest genetic variants associated with FH. We selected these regions of interest from the LDLR gene exons 4, 9 and 10, APOB exon 26 and PCSK9 exon 2 loci. Next, we amplified these regions of interest using conventional polymerase chain reaction. Finally, we sequenced the amplicons using paired-end Sanger sequencing and called variants from the chromatogram files using an in-house custom built bash script utilizing the open access program Tracy. Subsequently, we did quality checks on all reported pathogenic variant calls manually using Benchling's sequence alignment tool. We identified one pathogenic variant V523 M in the LDLR exon 10 region and report an FH prevalence of 1% (1/96), 95% CI: [0%,3.07%], in our Ghanaian cohort. Our finding underscores the importance of FH in driving ASCVD burden in Ghana and advocates the need for implementation science-driven programs to manage this genetic dyslipidemia in Ghana and SSA.