Methods of Diagnosing Cardiovascular Disease

Cardiovascular diseases like atherosclerosis are major causes of mortality and often occur as a complication of diabetes. Vascular dysfunction and atherosclerosis parallel the progression of diabetes and may be accelerated by factors such as hyperglycemia in individuals whose disease is poorly controlled. The inventions are based on the inventors’ discovery of single nucleotide polymorphisms (SNPs) in two genes that correlate with increased risk of cardiovascular disease. In one invention (JDP-092), the gene encodes the protein CD36, which is an 88 kDa membrane protein expressed on the surface of a wide variety of cell types, including adipocytes, skeletal muscle cells, platelets, and endothelial cells. CD36 is a class B scavenger receptor recognizing a variety of ligands including long-chain fatty acids and modified LDL, which has also been recently implicated as a regulator of the metabolic pathways involved in insulin resistance. In the other invention (JDP-102), the gene encodes the receptor for an important adipokine – adiponectin – that is correlated with increased risk of cardiovascular disease. Adiponectin is known to have direct protective effects on the arterial wall, and these anti-atherogenic effects are known to be modulated through the receptor in which these polymorphisms and haplotypes have been found. In the CD36 gene, five specific SNPs were analyzed and found to correlate to free fatty acid (FFA) levels and to risk of coronary artery disease (CAD). At three of these loci, men homozygous for one allele had 30% higher FFA levels than did men homozygous for the other allele. A significant association was also found between one particular CD36 haplotype and the incidence of CAD. In the adiponectin receptor gene, two specific SNPs were analyzed and found to correlate to risk of CAD in two specific populations (one from Boston, Mass. and one from Italy). Minor allele homozygotes for one of the SNPs had more than a two-fold increase in CAD risk across both populations. Homozygotes for a particular haplotype of the other SNP were 1.7-fold more likely to have had a myocardial infarction. In addition, homozygotes for the first SNP showed 30% lower levels of mRNA for the receptor than other subjects. These results point to sequence variants in this receptor as determinants of increased risk of cardiovascular disease Clinical & Commercial Utility: Both inventions feature diagnostic methods to detect an individual’s susceptibility to developing cardiovascular disease. This would be done by analysis of specific SNPs within the CD36 or adiponectin receptor gene that correlate to the disease risk. The invention therefore features methods of diagnosing or detecting susceptibility towards cardiovascular disease by typing specific SNPs in the genome of an individual
U.S. patent applications claiming both inventions have been filed. The research underlying JDP-092 is described in Ma, et al. (2004) Human Molecular Genetics, Vol. 13, No. 19, pages 2197–2205. The research leading to the JDP-102 invention has been published as Soccio, et al. (2006), Diabetes, Vol. 55, No. 10, pages 2763-2770.

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