Centre for Cardiovascular Genetics

Department of Medicine

Centre Director : Professor S.E. Humphries
Senior Academic Staff : Dr Philippa Talmud (Reader)
Dr David Flavell (Lecturer)

Description of Centre Activities:

Research focuses on identifying the inherited factors that contribute to an individuals's risk of developing coronary artery disease, and in the last year the centre has developed a number of new techniques that allow us to identify very rapidly the specific mutation in a gene of interest, and to carry out these tests up to 100 samples a week. We are now developing these methods to enable us to examine several thousand samples a week, which will allow us to complete some very powerful genetic analyses in the next year, using samples that have been collected through collaboration with clinical and epidemiological colleagues.

In the last year we have identified more than 20 mutations in the LDL-receptor gene in patients with familial hypercholesterolaemia, and in patients with familial combined hyperlipidaemia we have detected two common mutations in the gene for lipoprotein lipase, an enzyme that breaks down triglycerides in the blood. We have continued out work to identify mutations in genes that control the levels of proteins such as fibrinogen that cause the blood to clot and in genes that code for the structural components of the vessel wall, such as stromelysin. Studies are underway to look at the different response to drug treatment or to changes in the diet in patients with these different mutations and preliminary results are very encouraging. This suggests that further work may give information that will be helpful to develop therapeutic strategies that will be relevant to different individuals.

Current Research:

Study of candidate genes involved in determining risk of heart disease and levels of risk factor traits
Rapid Genotyping and Mutation Detection
Function of Promoter polymorphisms in candidate genes
Function of amino acid changes in candidate genes.
LDL-Receptor gene mutations in familial hypercholesterolaemia
Genetics of Dietary and postprandial effects
Gene and environment interaction

Staff Numbers: 20 Phd Student Numbers: 8


1 Fisher RM, Mailly F, Peacock RE, Hamsten A, Seed M, Yudkin JS, Beisiegel U, Feussner G, Miller G, Humphries SE, Talmud PJ. 1995) Interaction of the lipoprotein lipase asparagine 291 serine mutation with body mass index determines elevated plasma triacylglycerol concentrations: a study in hyperlipidaemic subjects, myocardial infarction survivors and healthy adults. J Lipid Res 36: 2104-2112.
2 Bolla MK, Haddad L, Humphries SE, Winder AF, Day INM (1995) A method for the rapid determination of hundreds of apoE genotypes, combining simplified, optimised protocols from sample acquisition to PCR and restriction digestion analysis by microplate array diagonal gel electrophoresis (MADGE). Clin Chem 41 (11) 1599-1604.
3 Montgomery HE, Clarkson P, Nwose OM, Mikalidis DP, Jagroop IA, Dollery C, Moult J, Benhizia F, Deanfield J, Jubb, World M, McEwan JR, Winder A, Humphries SE. (1996) The acute rise in plasma fibrinogen concentration with exercise is influenced by the G-453-A polymorphism of the beta-fibrinogen gene. Arterioslcr, Thromb, Vasc Biol 16: 386-391.
4 Ye S, Eriksson P, Hamsten A, Kirkinen M, Humphries SE, Henney AM. (1996) Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. Journal of Biological Chemistry 271: 13055-13060
5 Day INM, Whittall R, O'Dell S, Haddad L, Bolla M, Gudnason V, Humphries SE. Spectrum of LDL receptor gene mutations in heterozygous familial hypercholesterolaemia: towards molecular diagostics. Human Mutation - In press

Courses taught: None

Departmental Contact (academic):

Kathleen McCauley, secretary to Professor Humphries.

Department of Medicine
The Rayne Institute
University Street
Tel: 020 7679 7969/7962
Fax: 020 7679 6212
E-mail: rmhajac@ucl.ac.uk
Last updated on 18/10/00

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