Candidate gene polymorphism in cardiovascular disease: the BIP cohort.
BACKGROUND
Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprises 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, insulin, as well as clinical, demographic and lifestyle parameters.


OBJECTIVE
To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.


METHODS
DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n = 1480).


RESULTS
Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE(E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP(405val), ACE (Del), AGT (235thr), ELAM (128arg); P < 0001 and LPL (93G, 291Ser, 447ter); P < 005.


CONCLUSIONS
Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles--associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism--between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.
Molecular Genetics Laboratory, Alameda, California, USA. leshinsky@wolfson.health.gov.il
Esther
E
Leshinsky-Silver
Suzanne
S
Cheng
Michael A
MA
Grow
Schwartz
S
Shoshana
Leah
L
Scharf
Dorit
D
Lev
Mona
M
Boaz
Daniel
D
Brunner
Reuven
R
Zimlichman
D002318:Cardiovascular Diseases / Q000235:genetics* / Q000503:physiopathology; D018849:Controlled Clinical Trials as Topic; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015337:Multicenter Studies as Topic; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors