genetic causes of hypercholesterolaemia in the emirati population

Conditions: Familial Hypercholesterolemia

Summary: the scientific aims of the project are to understand the genetic basis of familial hypercholesterolaemia (fh) in the emirati population and estimate the overall prevalence of the disease. in addition, a clinical aim of the project is to explore the effectiveness of screening the relatives of individuals affected by fh and other lipid disorders ("cascade" screening) within emirati families.

familial hypercholesterolaemia is an inherited genetic disorder which causes elevated levels of low density lipoprotein (ldl) cholesterol in the blood. high ldl is a risk factor for with arterial disease and people with fh develop coronary artery disease (cad) early in life. people with only one inherited copy of the defective gene usually develop cad before the age of 60, whereas individuals who have inherited two copies usually die before the age of 30 from myocardial infarction ("heart attack") or sudden cardiac death. coronary artery disease is a major cause of death and disability in the united arab emirates (uae), and the medical costs associated with treating this condition are significant. early identification and treatment of affected individuals can substantially postpone the onset of arterial disease and reduce the risk of mortality. in clinical practice, fh cases are usually identified by screening the relatives of people known to be affected. current study will focus on identifying individuals with high risk score for fh, based on the available medical records and laboratory information system (lis). furthermore, patients with history of premature ischaemic vascular disease and/or high readings for ldl-c will be approached and asked to participate. the scientific aims of the study are: * identifying individuals with likelihood of fh diagnosis and confirming fh by genetic testing (applying next generation sequencing ngs technology to analyse the genes already known and/or suspected to cause fh). * identifying novel fh genes and mutations in the emirati population by performing whole exome and whole genome sequencing * validating positive genetic test results by performing mutational analysis on parental samples (if available) * introducing cascade screening on a clinical basis in order to identify affected relatives of those index individuals with a clinical diagnosis of fh * determining the prevalence of fh in the uae * determining the short and the long-term clinical outcomes of fh in the uae it is expected that the cascade screening will provide additional clinical benefit to study participants and their families in terms of early identification and treatment where diagnosis could otherwise be missed. early recognition and treatment in individuals with fh has been shown to reduce morbidity and mortality of affected individuals. the information gathered during this project will help introduce a cost-effective method for identifying people with dyslipidaemias and provide early intervention and management.

Eligibility criteria:
inclusion criteria: * patients attending imperial college london diabetes centre * patients with hypercholesterolaemia * patients with possible evidence of known premature coronary heart disease (chd) * patients (or parent/legal guardian if \<18 years) willing and able to give informed consent for participation in the study. exclusion criteria: * patients with no history of hypercholesterolaemia * patients or their legal guardian/legal representative who are unwilling or unable to give informed consent.

Keywords: familial hypercholesterolemia hypercholesterolemia cascade screening novel fh genes novel fh mutations next generation sequencing