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Genetic Polymorphisms Affect Concentrations of LDL

Researchers identify novel locus for low-density lipoprotein cholesterol on chromosome 1p13.3

FRIDAY, Feb. 8 (HealthDay News) -- Two genetic polymorphisms on chromosome 1p13.3 affect low-density lipoprotein (LDL) cholesterol concentrations, a discovery that may offer researchers new insights into the mechanisms of LDL regulation and lead to the development of new therapeutic agents for treating cardiovascular disease, according to study findings published in the Feb. 9 issue of The Lancet.

Manjinder S. Sandhu, Ph.D., of the University of Cambridge in Cambridge, U.K., and colleagues conducted genome-wide analyses of subjects from five large studies and performed replication studies in two independent populations.

The researchers' meta-analysis of data from all the studies showed that two autosomal single nucleotide polymorphisms (SNPs) at chromosomal locus 1p13.3 -- rs599839 and rs646776 -- explained around 1 percent of the variation in circulating LDL cholesterol concentrations and were associated with a mean change of about 15 percent in LDL cholesterol per allele.

"One of the SNPs at the chromosome 1p13.3 locus was associated with a 20 percent lower risk of myocardial infarction. This decrease is much larger than would be predicted from the level of LDL lowering, and therefore other effects of the chromosome 1p13.3 polymorphism might be involved," states the author of an accompanying editorial. "In addition to the identification of new treatment targets, the discovery of genetic polymorphisms that affect LDL and other markers of cardiovascular disease risk could provide a means to categorize specific phenotypes that might merit different treatments and to identify at-risk individuals."

GlaxoSmithKline provided financial support for the study and several of the authors report financial affiliations with pharmaceutical companies, including GlaxoSmithKline.

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