Principal Investigators:
Chaim Lotan MD, Arthur Pollak MD, Tova Chajek MD, Gideon Friedman MD

Abstract
Elevated levels of circulating homocysteine are common in patients with occlusive vascular disease. Homocysteine, a sulfurated amino acid, is metabolized by re-methylation and trans-sulfuration. In re-methylation, the primary methyl donor for the vitamin B12 (methyl-cobalamine)-dependent conversion of homocysteine to methionine is 5-methyl-tetra-hydrofolate, synthesized by 5,10-methylene-tetra-hydrofolate-reductase (MTHFR) from 5,10-methylene-tetra-hydrofolate. Conversion of homocysteine to methionine keeps the former at non-toxic levels in the plasma. In the trans-sulfuration pathway, homocysteine condenses with serine to form cystathionine in an irreversible reaction, catalyzed by the pyridoxal 5-phosphate (PLP)-containing enzyme, cystathionine B-synthase (CBS).
A number of enzymes involved in the re-methylation-pathway such as MTHFR have recently been shown to be polymorphic. Homozygous carriers of any of these polymorphisms may show an increased risk of developing atherosclerosis. We propose to screen a cohort of Israeli women, at ages 40-75, with coronary artery disease (CAD), for the presence of both the C677?T transition and the A1298?C transversion in the MTHFR-gene.
All women will be examined for their fasting glucose and insulin levels, glycated hemoglobin and serum proteins, TC, TG, LDL-C, HDL-C, urea, creatinine and plasma homocysteine levels. All subjects will complete an extensive general socio-demographic and health questionnaire, including data on family history, current use of medications (including vitamins), smoking history, alcohol and dietary consumption, as well as physical activity.
Results of this study will allow a better understanding of the genetic influence on homocysteine levels leading to CAD in the Israeli female population. Due to the fact that elevated serum homocysteine levels can be prevented by food additives (e.g.folic acid), preventive treatment may be specifically targeted to those women having a genetic pre-disposition.

Status: Recruitment of patients