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Jan 14, 2008

Scientists Find Novel Variants Associated with Lipid Levels

  • A genome-wide scan found 18 loci associated with levels of lipids, cholesterol, and triglycerides, according to an international group of researchers. They say that six of these represent DNA regions previously unassociated with the traits. The findings are published in the January 13 advance online issue of Nature Geneitcs.

    The investigators scanned the genomes of 8,816 people. This included 2,758 individuals from the Diabetes Genetics Initiative (DGI) specific to the current paper, 1,874 individuals from the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study of type 2 diabetes, and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in the same issue of Nature Genetics. Targeted replication association analyses in up to 18,554 independent participants was also performed, according to the research team.

    This work produced a list of comon SNPs reproducibly associated with levels of LDL cholesterol, HDL cholesterol, or triglycerides at 18 loci. Twelve of the loci were already known to influence lipid levels. The remaining six reportedly turned out to be entirely new: two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1, and SORT1 as well as 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2), and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2, and PBX4 as well as 1p31 near ANGPTL3).

    The study identified many of the established and emerging targets for drug therapy such as the HMGCR gene, which is a target of statin medications, and the PCSK9 gene, according to the scientists. They say that one of the six, 1p13, altered the expression of three nearby genes. A proxy of 1p13 was reportedly shown to be associated with coronary artery disease.

    The second companion study discovered more than 25 genetic variants in 18 genes connected to cholesterol and lipid levels. They say that seven of the 18 genes previously had not been connected to these levels, while the 11 others confirm previous discoveries.

    The second group of researchers were able to identify variations in 18 genes that influence HDL, LDL, and/or triglyceride levels. To determine if the genetic variants associated with lipid levels also influence risk of heart disease, the scientists compared their results with data from the Wellcome Trust Case Control Consortium’s recent study of coronary artery disease (CAD) involving 15,000 British individuals.

    They found that all gene variants associated with increased LDL levels were more prevalent among people with CAD. Those with the gene variant for high triglyceride levels also had an increased risk for CAD, although the relationship was not as strong, according to the researhcers. No relationship was found between HDL and CAD.

    Both studies involved a combined effort from a wide variety of international researchers.



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