Baboon Study Suggests Cancer-Related Genes Regulate LDL Cholesterol Levels

Genome analysis of baboons in a controlled feeding study identified four genes linked to control of the level of serum low-density lipoprotein cholesterol (LDL-c), a biomarker for risk of cardiovascular disease.

Investigators at the Texas Biomedical Research Institute (San Antonio, USA) had previously identified a cluster of quantitative trait loci (QTL) on baboon chromosome 11 for multiple related quantitative traits for serum LDL-c. In the current study, they determined the level of LDL-c in the 1,500 animals in their baboon colony and selected three baboons with low LDL-c levels and three with high levels. The baboons were fed a high-cholesterol, high fat (HCHF) diet for seven weeks, after which hepatic whole genome expression profiling for LDL-c was performed.

Results published in the April 17, 2013, online edition of the Journal of Lipid Research revealed that three genes were differentially expressed in the low LDL-c animals and eight in high LDL-c animals in response to the HCHF diet. Seven genes (ACVR1B, CALCOCO1, DGKA, ERBB3, KRT73, MYL6B, and TENC1) showed discordant expression between the low and high LDL-c baboons.

Data obtained with gene array and high throughput sequencing technology enabled integration of microRNA (miRNA) and messenger RNA (mRNA) expression profiles, which showed that four candidate genes (ACVR1B, DGKA, ERBB3, and TENC1) were miRNA targets and that the miRNAs were inversely expressed to the target genes. The four genes are members of a signaling pathway known to be important for cell survival, and disruption of this pathway due to mutations in these genes has been associated with some types of cancer.

"Our findings are important because they provide new targets for the development of novel drugs to reduce heart disease risk in humans," said senior Dr. Laura Cox, associate scientist in genetics at the Texas Biomedical Research Institute. "Since these genes have previously been associated with cancer, our findings suggest that genetic causes of heart disease may overlap with causes of some types of cancer. That starts to give us the specific targets for new therapies. If all goes well, this information may be available within two years."

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Texas Biomedical Research Institute