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Risk of Cholesterol Elevated by the Presence of Single Letter in Human Genome
Led by Rockefeller University scientists, the consortium says that the letter they have identified is linked with elevated LDL cholesterol levels, one of the leading health concerns.
Research leader Jan L. Breslow, head of the Laboratory of Biochemical Genetics and Metabolism, says that this study brings a new level of understanding to an enzyme called HMGCR, the rate-limiting catalytic engine of cholesterol biosynthesis and the target of the much-revered cholesterol-lowering drugs known as statins.
For years, HMGCR has been known to play a key role in cholesterol metabolism. However, there was no evidence that common genetic variants existed in the gene that could affect how people metabolise cholesterol, an artery-clogging fat when produced (or consumed) in excess.
"In fact, HMGCR became the poster boy for how genes without common variation can still be good drug targets," Science Daily quoted first author Ralph Burkhardt, a postdoctoral fellow in the Breslow lab, as saying.
The researchers have revealed that their current study builds upon ongoing research involving the inhabitants of the Micronesian island of Kosrae, who have a higher burden of risk factors associated with obesity and heart disease.
Burkhardt, Breslow and their colleagues took advantage of the growing power of genomic databases and genetic and biochemical techniques to show that a single letter difference, known as a single nucleotide polymorphism or SNP, in the HMGCR gene was linked to higher LDL cholesterol levels in the 4,947 people whose blood was analysed: a population of 2,346 Kosraeans and a European sample that was included for statistical power.
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