Impact of genetic testing on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia (GenTLe-FH): a randomised waiting list controlled open-label study protocol

Abstract

IntroductionFamilial hypercholesterolemia (FH) is an autosomal-dominant inherited genetic disease. High-throughput sequencing quickly and comprehensively detects causative variants of FH-related genes (LDLR, PCSK9, APOB and LDLRAP1). Although the presence of causative variants in FH-related genes correlates with future cardiovascular events, it remains unclear whether detection of causative gene mutation and disclosure of its associated cardiovascular risk affects outcomes in patients with FH. Therefore, this study intends to evaluate the efficacy of counselling future cardiovascular risk based on genetic testing in addition to standard patients’ education programme in patients with FH.Methods and analysisA randomised, waiting-list controlled, open-label, single-centre trial will be conducted. We will recruit patients with clinically diagnosed FH without previous history of coronary heart disease from March 2018 to December 2019, and we plan to follow up participants until March 2021. For the intervention group, we will perform genetic counselling and will inform an estimated future cardiovascular risk based on individuals’ genetic testing results. The primary endpoint of this study is the plasma low-density lipoprotein cholesterol level at 24 weeks after randomisation. The secondary endpoints assessed at 24 and 48 weeks are as follows: blood test results; smoking status; changes of lipid-lowering agents’ regimen and Patients Satisfaction Questionnaire Short Form scores among the four groups divided by the presence of genetic counselling and genetic status of FH.Ethics and disseminationThis study will be conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects and all other applicable laws and guidelines in Japan. This study protocol was approved by the IRB at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.Trial registration numberUMIN000029375.

Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design

“…We are also now conducting another clinical trial (Impact of Genetic Testing on LDL Cholesterol in Patients with FH (GenTLe-FH)), which aims to assess the clinical benefits of genetic testing in FH subjects. 18 Our studies may provide interesting perspectives in returning genetic results with the disclosure of future ASCVD risk for patients with FH, and providing them with reliable and evidence-based treatment options to reduce their risk. We may associate our initiative in time with another Japanese FH registry, the PROLIPID-FH registry.…”

Case Report: Hypertriglyceridemia and Premature Atherosclerosis in a Patient With Apolipoprotein E Gene ε2ε1 Genotype

“…Such non-clinical consequences of genetic testing are labeled as patient empowerment ( 31 ). How genetic testing influences the individual's adherence to the given recommendations has been investigated among familial hypercholesterolemia patients ( 32 , 33 ), but no evidence is available for familial dysbetalipoproteinemia. It is of note, that women have another important risk factor for developing hypertriglyceridemia, over and above, unhealthy lifestyle habits.…”

SOAT1 methylation is associated with coronary heart disease

“…Some researchers have observed that hypercholesterolemia can cause multiple physiologic outcomes, such as coronary artery disease, diabetes and obesity [26, 27]. SOAT1 is an important protein for regulating cholesterol absorption and it plays a pivotal role in the development of atherosclerosis.…”