Hapizah Md Nawawi1,2, Yung-An Chua1, Gerald F Watts3. 1. Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM). 2. Specialist Lipid and Coronary Risk Prevention Clinics, Clinical Training Centre, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia. 3. Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital; School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
Abstract
PURPOSE OF REVIEW: With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice. RECENT FINDINGS: Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Hypertriglyceridaemia may be caused by rare recessive monogenic, or by polygenic, gene variants; genetic testing may be useful in the former, for which antisense therapy targeting apoC-III has been approved. Familial high-density lipoprotein deficiency is caused by specific genetic mutations, but there is no effective therapy. Familial combined hyperlipidaemia (FCHL) is caused by polygenic variants for which there is no specific gene testing panel. Familial dysbetalipoproteinaemia is less frequent and commonly caused by APOE ε2ε2 homozygosity; as with FCHL, it is responsive to lifestyle modifications and statins or/and fibrates. Elevated lipoprotein(a) is a quantitative genetic trait whose value in risk prediction over-rides genetic testing; treatment relies on RNA therapeutics. SUMMARY: Genetic testing is not at present commonly available for managing dyslipidaemias. Rapidly advancing technology may presage wider use, but its worth will require demonstration of cost-effectiveness and a healthcare workforce trained in genomic medicine.
PURPOSE OF REVIEW: With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice. RECENT FINDINGS: Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Hypertriglyceridaemia may be caused by rare recessive monogenic, or by polygenic, gene variants; genetic testing may be useful in the former, for which antisense therapy targeting apoC-III has been approved. Familial high-density lipoprotein deficiency is caused by specific genetic mutations, but there is no effective therapy. Familial combined hyperlipidaemia (FCHL) is caused by polygenic variants for which there is no specific gene testing panel. Familial dysbetalipoproteinaemia is less frequent and commonly caused by APOE ε2ε2 homozygosity; as with FCHL, it is responsive to lifestyle modifications and statins or/and fibrates. Elevated lipoprotein(a) is a quantitative genetic trait whose value in risk prediction over-rides genetic testing; treatment relies on RNA therapeutics. SUMMARY: Genetic testing is not at present commonly available for managing dyslipidaemias. Rapidly advancing technology may presage wider use, but its worth will require demonstration of cost-effectiveness and a healthcare workforce trained in genomic medicine.
Authors: Al'aina Yuhainis Firus Khan; Anis Safura Ramli; Suraya Abdul Razak; Noor Alicezah Mohd Kasim; Yung-An Chua; Ahmad Zia Ul-Saufie; Mohd Amin Jalaludin; Hapizah Nawawi Journal: Int J Environ Res Public Health Date: 2022-09-19 Impact factor: 4.614