New Heart Disease Markers Discovered

(Page 2)

Using genetic material and data stemming from three separate cardiovascular studies that comprised more than 12,000 individuals, the groups scanned for genetic differences that correlated with elevated CRP levels. Their tools were DNA microarrays -- glass slides, about the length and width of a stick of gum, which can probe more than 300,000 individual genetic variants per individual. Reiner's team also employed a candidate gene approach, looking specifically at polymorphisms in specific genes the scientists thought might play a role.

The teams found seven genomic regions that appeared to be strongly correlated with CRP levels. Six of those regions contained genes associated in one way or another with metabolic syndrome; the seventh contained no known genes. These six genomic locations read like a Who's Who of cardiovascular disease and metabolic disorder, genes such as HNF1A, which regulates the CRP gene; the leptin receptor, which regulates weight; a regulator of glucose metabolism; and apolipoprotein E.

"I think it's quite interesting that genes involved with traits of metabolic syndrome are also associated with CRP," said Dr. Caroline Fox, medical officer of the National Heart, Lung, and Blood Institute. "I think that's the most fascinating aspect of this paper."

"From our perspective, it's an incredibly satisfying finding," said Ridker. "Often when you do genome-wide association studies, you get genes that you don't understand. In this case, we found a gene cluster that makes perfect sense."

Scott, who has performed similar (albeit unpublished) analyses, said he believed the findings. "We basically replicate all of those loci, the headline loci anyways," he said. "I'm sure it's right, absolutely."

According to Ridker, "The 'Aha' moment was recognizing that these six or seven genes are all interrelated to these metabolic pathways. The question is, I know CRP predicts heart attack and stroke, and these genes are related to CRP. Do these provide clues to what the proper interventions might be? And we think the answer is yes."