Authors: Wierzbicki, Anthony S.; Graham, Colin A.; Young, Ian S.; Nicholls, D. P.

Source: Current Vascular Pharmacology, Volume 6, Number 1, January 2008 , pp. 13-22(10)

Publisher: Bentham Science Publishers

Abstract:

Familial combined hyperlipidaemia (FCH) was identified in early genetic studies of populations as a dominant condition associated with mixed hyperlipidaemia and early onset coronary heart disease. Later studies extended the phenotype and noted that this genetic hyperlipidaemia was sensitive to environmental effects. This article reviews the definitions, animal models and genetics of FCH.

In contrast to familial hypercholesterolaemia, which is caused by mutations in a limited number of affected genes, the genetics of FCH have remained obscure and very few definite candidate genes have been identified. A strong role for the apoA-I, A-IV, A-V, C-III cluster on chromosome 11 was identified early on and multiple associations have been found to hyperlipidaemia in this region and more strongly to adjacent sections of the chromosome. More recently quantitative trait mapping has identified a number of candidate genes including upstream transcription factor -1 (USF-1) on 1 q21 and CD- 36 on chromosome 4. Of these the strongest evidence, based on 4 analyses, links the lipid components of FCH to intronic variants in the USF-1 gene on chromosome 1q21-23. Unfortunately USF-1 yet fails to show clear associations with diabetes and the metabolic syndrome which co-map to this region and are also associated with mixed hyperlipidaemia. Large scale validation of USF-1 variants in other populations is still awaited.

It is likely that FCH is a heterogeneous condition, that is subject to wide-scale environmental confounding from common traits such as obesity and the metabolic syndrome, and that the resolution of its genetics is going to prove a severe challenge.

Keywords: Familial combined hyperlipidaemia; genetics; insulin resistance; triglyceride; colesterol

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157016108783331268

Publication date: 2008-01-01

More about this publication?

• Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.
  
  Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.
  
  Debates will also be encouraged in the correspondence section of this journal.

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