UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES

Discovery of New Genotypes Associated with Dyslipidemia

Starting with the description of the phenotype of normotriglyceridemic abetalipoproteinemia and the later demonstration that it is based on a mutation in the gene for apolipoprotein B-100, I have been involved in the description of a number of newly emerging genetic disorders leading to dyslipidemia. One is a form of hypertriglyceridemia related to a mutation in apolipoprotein C-III. Several others lead to the phenotypes of hypobetalipoproteinemia. A prevalent disorder results in ligand-defective hypercholesterolemia (apo B Arg 3500 Cys). Most recently, I have been involved in the elucidation of a new form of combined hyperlipidemia, due to mutations in the gene for cholesterol 7 alpha hydroxylase. This disorder is thought to affect at least one hundred thousand Americans.

Identification of Novel Genes for Coronary Artery Disease and Stroke

I have had a major role in a genome scale effort to detect gene polymorphisms that are associated with stroke and coronary disease, including myocardial infarction. To date over 11,000 gene loci have been scanned, yielding 21 significant gene associations with coronary disease and 4 with stroke.

Selected References

Duchateau, P.N., Movsesyan, I., Yamashita, S., Sakai, N, Hirano, K-I, Schoenhaus, S., O'Connor-Kearns, P.., Spencer, S.J., Jaffe, R.B., Redberg, R.F., Ishida, B.Y., Matsuzawa, Y., Kane, J.P., Malloy, MJ,. Plasma apolipoprotein L concentrations correlate with plasma triglycerides and cholesterol levels in normolipidemic, hyperlipidemic and diabetic subjects. J. Lipid Res. 41:1231, 2000.

Pullinger, C. R. Eng, G. Salen, S. Shefer, A. K. Batta, S. K. Erickson, A. Verhagen, C.R. Rivera, S.J. Mulvihill, MJ. Malloy, J P. Kane. Human Cholesterol 7-Hydroxylase (CYP7A1) Deficiency has a Hypercholesterolemic Phenotype. J. Clin. Invest . 110:109-17, 2002.

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