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Scientists associate 6 new genetic variants with heart disease risk factor
Date:1/13/2008

ct future risk of heart attack and are known to be influenced by both genetic and lifestyle factors. Similarly, the amount of triglycerides in the blood is also determined by a mix of genes and lifestyle and is often considered a marker of type 2 diabetes risk, another important contributor to heart disease.

To systematically identify genetic variants associated with blood lipid levels, Kathiresan and his colleagues scanned the genomes of over 27,000 people to locate common single-letter variations called single nucleotide polymorphisms (SNPs). This work produced a list of 18 SNPs reproducibly associated with levels of LDL cholesterol, HDL cholesterol, or triglycerides. Twelve of the SNPs were already known to influence lipid levels, underscoring the power of the genome scanning technique to find key genes. Importantly, the remaining six SNPs turned out to be entirely new: two are associated with LDL cholesterol, one with HDL cholesterol, and five with triglycerides.

Kathiresan and his colleagues took the study a step further, quantifying how a single-letter change in the genetic sequence can influence the amount of lipids in the blood. For example, someone who carries a T at a particular spot on both copies of chromosome 19 can have an LDL cholesterol level that is 16 mg/dL lower than someone who carries the more common G. With an average LDL cholesterol level of roughly 130 mg/dL in adults, this may seem like a relatively minor change, but when many genetic variants 18 from this study alone come into play, they can add up to large differences among people, explained Kathiresan.

Importantly, the study identified many of the established and emerging targets for drug therapy, such as the HMGCR gene, which is a target of so-called statin medications that lower LDL cholesterol, and the PCSK9 gene. This suggests that some of the newly identified gene regions may eventually become new targets for drug therapy.

Additionally, the rese
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Contact: Leah Eisenstadt
leah@broad.mit.edu
617-324-2619
Broad Institute of MIT and Harvard
Source:Eurekalert

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