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Published on: September 15, 2018
Genetic dissection of familial combined hyperlipidemia
P M Eurlings1, C J van der Kallen, J M Geurts
1Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands.
Insights
Familial combined hyperlipidemia (FCHL) is a common genetic disorder. Research reviews strategies to understand its complex genetics and identify contributing genes for better disease management.
Area of Science:
- Cardiovascular Genetics
- Human Genetics
- Lipid Metabolism
Background:
- Familial combined hyperlipidemia (FCHL) is the most prevalent genetic hyperlipidemia.
- FCHL is associated with premature coronary heart disease (CHD) in individuals under 60.
- Despite being identified 25 years ago, the FCHL phenotype and its complex genetics remain incompletely understood.
Purpose of the Study:
- To review genetic strategies for dissecting the complex genetic background of FCHL.
- To explore methods for identifying genes contributing to the FCHL phenotype.
- To advance the understanding of FCHL's heterogeneous genetic basis.
Main Methods:
- Review of genetic linkage studies.
- Review of association studies.
- Review of differential gene expression studies.
- Discussion of human and animal model approaches.
Main Results:
- The genetics of FCHL are complex and likely heterogeneous, not a simple dominant inheritance.
- Combined genetic approaches (linkage, association, gene expression) are effective for complex diseases.
- Animal models and human studies offer complementary insights.
Conclusions:
- Understanding FCHL genetics requires sophisticated and integrated approaches.
- Identifying specific genes is crucial for unraveling FCHL's complex inheritance patterns.
- Further research using these strategies will clarify FCHL's genetic architecture.
Abstract:
Familial combined hyperlipidemia (FCHL) is the most common genetic hyperlipidemia in man. FCHL is characterized by familial clustering of hyperlipidemia and clinical manifestations of premature coronary heart disease, i.e., before the age of 60. Although FCHL was delineated about 25 years ago, at present the FCHL phenotype and its complex genetics are not fully understood. Initially, the familial aggregation of high plasma total cholesterol and triglyceride levels, with a bimodal distribution of triglycerides, was taken as evidence of a dominant mode of inheritance. However, it is now clear that the genetics of FCHL is more complex, and it has been suggested that FCHL is heterogeneous. Several approaches can be taken to identify genes contributing to the disease phenotype in complex genetic disorders either by studying the disease in the human situation or by using animal models. Recent reports have shown that a combination of genetic linkage studies, association studies, and differential gene expression studies provides a useful tool for the genetic dissection of complex diseases. Therefore, the genetic strategies that will be used to dissect the genetic background of FCHL are reviewed.
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