Genetics

Fifth Cholesterol Gene Found: Fifth gene known to cause elevated cholesterol when it is defective. The gene's product is an enzyme called cholesterol 7-alpha hydroxylase (CYP7A1), and it is essential for the normal elimination of cholesterol. The enzyme initiates the primary conversion of cholesterol into bile acids in the liver. J Clin Investigation 7/02, UCSF

Gene associatedwith Early CAD: Circulation 8/6/02. Dutch study shows that a specific mutation in a gene called ABCC6 was more common in people who developed coronary artery disease before age 50 than among healthy people. The mutation is called R1141X. It can be inherited or occur spontaneously. ABCC6 is in a family of genes called the adenosine triphosphate binding cassette genes. Genes in this family code for proteins that transport molecules into and out of cells. Researchers have not yet discovered the function of the ABCC6 gene; they theorize that it most likely plays a role in keeping elastic fibers healthy. The mutated ABCC6 gene causes pseudoxanthoma elasticum (PXE), a rare disorder of the connective tissue in the skin, retina and artery walls that occurs in about 1 in 100,000 people. PXE causes the breakdown of elastic fibers and tissues become hardened with calcium. Cardiovascular signs of PXE include premature coronary artery disease caused by elastic fibers calcifying in the arteries. The R1141X is the most frequent mutation found in the ABCC6 gene. Possession of a single recessive gene found in 3.4% of individuals with heart disease before age50, a four fold increase.

ACE Gene Deletion Associated with Enlarged L Ventricle in Athletes: Hearts of athletes who had two copies of the D (deletion) form of the angiotensin-converting enzyme (ACE) gene grew more in response to exercise than the hearts of other athletes with 1 D allele and one I (insertion) allele. 8/6/03 Journal of the American College of Cardiology. 61 male athletes, aged 25 to 40, with similar fitness training backgrounds. Ultrasound was used to measure the size of their hearts. The researchers found the DD genotype was associated with a higher left ventricular mass index than the ID genotype. Association between left ventricular mass and DD genotype was seen regardless of other known biologic factors which may influence cardiac growth, such as age, hemoglobin levels, years of training, body mass index and blood pressure. Dr. Domingo Hernandez, Spain.

Klotho Gene Double Atherosclerosis: SIBS-I, included 520 apparently healthy siblings of hospitalized patients, and 97 of them were discovered to have undetected atherosclerosis. The other, called SIBS-II, included only African Americans and found that 56 of 436 participants had undetected atherosclerosis. For the SIBS-I group, roughly 15 percent of the 373 participants with two "good" copies of klotho had undetected atherosclerosis. Of the 135 people with one copy of the KL-VS version of klotho, about 25 percent had hidden coronary artery disease, as did about 40 percent of the 12 people with two copies of KL-VS. Similar results were seen for SIBS-II. Johns Hopkins, Hal Dietz, 5/03 Am J Hum Genetics.

Biochemistry

Endothelins: Main heart endothelin is ET-1, a powerful vasoconstrictor. ET-1 imp in early stages of atherosclerosis attracting monocytes and macrophages and causing enthelial dysfunc. Also up in MIs and Prinzmetal as well as some others. Blockers ETA & ETB in development.