Projects / Programmes
Genetics and clinical characteristics of hypercholesterolomia in children and adolescents
| Code |
Science |
Field |
Subfield |
| 3.05.00 |
Medical sciences |
Human reproduction |
|
| Code |
Science |
Field |
| B660 |
Biomedical sciences |
Pediatrics |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
Familiar hypercholesterolemia, genetic diagnostics, pharmacogenetics, population screening, atherosclerosis, prognostic factors
Researchers (20)
Organisations (2)
Abstract
Hypercholesterolemia (HCH) is considered to be one of the main risk factors for the development of the atherosclerosis (ATS) and cardiovascular disease (CVD), which could be substantially modified; the only condition is to recognize and to treat it in time. In the great majority of the cases, the etiology of the HCH is polygenic. Much rarer is the monogenic HCH, which mostly is heterozygous familial HCH (FH), its frequency is estimated to be 1 in 500 people. In Slovenia there is - according to the available data unique in the world - a nation wide population screening for the HCH (at the age of five), which enables early recognition and treatment of the children with HCH.
But the definitive diagnostics of the FH will be possible only after the implementation of the genetic diagnostics (LDLR, APOB, PCSK9 genes mutations can cause FH). The diagnosis of the FH is especially important in children and adolescents because most of them are clinically asymptomatic; frequently they have yet unexpressed or unreliable family history; they are the target group for the primary preventive of ATS and CVD. The implementation of the genetic diagnostics will enable us to found the national registry of the FH patients where also the adult relatives of the children and adolescents with the FH will be included. That will in the next step enable us to study the prognostic value of the specific genetic, laboratory and clinical characteristics of the patients with the FH, and to assess the effectiveness of the population screening of the HCH for the identification of patients with the FH. The genetic diagnostics will be broadened to analyze also pharmacogenetic variability, which could be used to guide statin therapy and increase its safety in clinical practice, which is especially important for the FH patients which usually need life-long therapy.
Significance for science
The thorough evaluation of genetic background in this relatively large and clinically well determined cohort of patients with hypercholesterolemia is bringing important new basic knowledge on aetiology of the familiar hypercholesterolemia as well as provide further new clinically relevant knowledge. Slovenia is the only country worldwide where population screening for hypercholesterolemia (HH) in 5 years old children enables early identification and treatment of the disease. Genetic data is showing the screening program for HH to be effective in detection of FH. We demonstrated the necessity of universal screening for diagnosing and management of children with familial hypercholesterolemia, including the the children with mildly elevated total cholesterol values and negative family history. Nevertheless, detection of familial hypercholesterolemia in primary care with biochemical screening followed by endocrinological evaluation and targeted next generation screening at the tertiary institution is affective and affordable strategy.
Significance for the country
The study is exstensively supplementing basic knowledge and is bringing clinically relevant new knowledge enabling early identification of paediatric individuals at higher risk for development of arthrosclerosis and cardiovascular diseases. Therefore, early prevention of complications development and late sequelae would be possible. The study may: • improve the medical service provided to patients with familiar hypercholesterolemia, and further early treatment and prevention of atherosclerosis and cardiovascular diseases as leading cause of morbidity in developed world • increase the quality of life of patients and their families; • decrease the amount of working days lost by the caregivers; • decrease of direct and indirect costs related to this pathology. Furhermore, the results are showing the screening program for HH to be effective in detection of FH. This is assigning Slovenia as the leading county in the early identification of hypercholesterolemia, since it is the only country worldwide with this kind of population screening.
Most important scientific results
Annual report
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2011,
2012,
2013,
final report,
complete report on dLib.si
