AUTHOR=Rimbert Antoine , Daggag Hinda , Lansberg Peter , Buckley Adam , Viel Martijn , Kanninga Roan , Johansson Lennart , Dullaart Robin P. F. , Sinke Richard , Al Tikriti Alia , Kuivenhoven Jan Albert , Barakat Maha Taysir 

TITLE=Low Detection Rates of Genetic FH in Cohort of Patients With Severe Hypercholesterolemia in the United Arabic Emirates

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.809256

DOI=10.3389/fgene.2021.809256

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Programs to screen for Familial hypercholesterolemia (FH) are conducted worldwide. In Western societies, these programs have been shown to be cost-effective with hit/detection rates of 1 in 217–250. Thus far, there is no published data on genetic FH in the Gulf region. Using United Arab Emirates as a proxy for the Gulf region, we assessed the prevalence of genetically confirmed FH in the Emirati population sample.</p><p><bold>Materials and Methods:</bold> We recruited 229 patients with LDL-C &gt;95<sup>th</sup> percentile and employed a customized next generation sequencing pipeline to screen canonical FH genes (<italic>LDLR, APOB, PCSK9, LDLRAP1</italic>).</p><p><bold>Results:</bold> Participants were characterized by mean total cholesterol and low-density lipoprotein cholesterol (LDL-c) of 6.3 ± 1.1 and 4.7 ± 1.1 mmol/L respectively. Ninety-six percent of the participants were using lipid-lowering medication with mean corrected LDL-c values of 10.0 ± 3.0 mmol/L 15 out of 229 participants were found to suffer from genetically confirmed FH. Carriers of causal genetic variants for FH had higher on-treatment LDL-c compared to those without causal variants (5.7 ± 1.5 vs 4.7 ± 1.0; <italic>p</italic> = 3.7E-04). The groups did not differ regarding high-density lipoprotein cholesterol, triglycerides, body mass index, blood pressure, glucose, and glycated haemoglobin.</p><p><bold>Conclusion:</bold> This study reveals a low 7% prevalence of genetic FH in Emiratis with marked hypercholesterolemia as determined by correcting LDL-c for the use of lipid-lowering treatment. The portfolio of mutations identified is, to a large extent, unique and includes gene duplications. Our findings warrant further studies into origins of hypercholesterolemia in these patients. This is further supported by the fact that these patients are also characterized by high prevalence of type 2 diabetes (42% in the current study cohort) which already puts them at an increased risk of atherosclerotic cardiovascular disease. These results may also be useful in public health initiatives for FH cascade screening programs in the UAE and maybe the Gulf region.</p>