Genetic polymorphisms associated with cardiovascular diseases, methods of detection and uses thereof

Abstract

The present invention provides compositions and methods based on genetic polymorphisms that are associated with cardiovascular diseases, particularly coronary heart disease (especially myocardial infarction) or hypertension. For example, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by these nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and variant proteins, and methods of using the nucleic acid molecules and proteins as well as methods of using reagents for their detection.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application of U.S. non-provisional application Ser. No. 12 / 500,378, filed on Jul. 9, 2009, which claims priority to U.S. provisional application Ser. No. 61 / 134,522, filed on Jul. 9, 2008, the contents of each of which are hereby incorporated by reference in their entirety into this application.FIELD OF THE INVENTION[0002]The present invention is in the field of cardiovascular diseases (CVD), particularly coronary heart disease (CHD), including myocardial infarction (MI), and hypertension. In particular, the present invention relates to specific single nucleotide polymorphisms (SNPs) in the human genome, and their association with CVD. The SNPs disclosed herein can be used as targets for the design of diagnostic reagents and the development of therapeutic agents, as well as for disease association and linkage analysis. In particular, the SNPs of the present invention are useful for such uses as identifyin...

AI Technical Summary

Benefits of technology

The present invention provides methods for determining whether to use a treatment (such as statin) for individuals with CVD or at risk of developing CVD. The methods also include selecting the optimal treatment regime and determining the likelihood of side effects from the treatment. The invention also provides methods for selecting individuals for a therapeutic trial of a statin based on their genotype and reducing an individual's risk of developing CVD or hypertension by using a statin treatment.

Problems solved by technology

The luminal narrowing or blockage of coronary arteries reduces oxygen and nutrient supply to the cardiac muscle (cardiac ischemia), leading to myocardial necrosis and / or stunning.

A vulnerable plaque is a plaque, often not stenotic, that has a high likelihood of becoming disrupted or eroded, thus forming a thrombogenic focus.

However, due to the asymptomatic nature of 25% of acute MIs (absence of atypical chest pain, low ECG sensitivity), a significant portion of MIs are not diagnosed and therefore not treated appropriately (e.g., prevention of recurrent MIs).

These markers have significant limitations such as low specificity and low positive predictive value, and the need for multiple reference intervals to be used for different groups of people (e.g., males-females, smokers-non smokers, hormone replacement therapy users, different age groups).

These limitations diminish the utility of such markers as independent prognostic markers for MI screening.

Individuals who experience early-onset MI may not be effectively identified by current cholesterol treatment guidelines, such as those suggested by the National Cholesterol Education Program.

The resultant increase in LDL catabolism results in decreased circulating LDL, a major risk factor for cardiovascular disease.

Additionally, the effects of a variant form may be both beneficial and detrimental, depending on the circumstances.

For example, a heterozygous sickle cell mutation confers resistance to malaria, but a homozygous sickle cell mutation is usually lethal.

A nonsense mutation results in a type of non-synonymous codon change in which a stop codon is formed, thereby leading to premature termination of a polypeptide chain and a truncated protein.

Furthermore, in the case of nonsense mutations, a SNP may lead to premature termination of a polypeptide product.

Such variant products can result in a pathological condition, e.g., genetic disease.

Clinical trials have shown that patient response to treatment with pharmaceuticals is often heterogeneous.

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