title: Relationship of eNOS gene variants to diseases that have in common an endothelial cell dysfunction.
abstract: The endothelial cell (EC) dysfunction is a common characteristic of various pathologies that include atherosclerosis, hypertension, and Fabry's disease. Aware of the role of eNO and ACE in EC dysfunction, we questioned whether polymorphism of eNOS and/or ACE gene may be a common denominator in these pathologies. Patients with CHD (108), HT (109), Fabry's disease (37) and healthy subjects (control, 141) were genotyped for the eNOSG894T by RFLP-PCR technique and for eNOS4b/a, and ACEI/D polymorphisms by PCR amplification. The results of these studies were statistically evaluated. Compared to controls, the frequency of the eNOSG894T (T allele) was higher in CHD (P=0.03) and Fabry (P=0.01), while the eNOS4b/a (a allele) in CHD (P=0.01) and HT patients (P=0.01). The proportion of the ACEI/D was similar in all subjects. In CHD patients at "low risk" of atherogenic factors, the frequency of the T and a alleles of eNOS gene was high (P=0.03 and 0.02, respectively). Carriers of the T allele of eNOSG894T were over-represented (P=0.04) in Fabry subgroup with renal failure. Compared to women, the eNOS894T alleles were more frequent (P=0.03) in men with CHD and HT, whereas ACE I/D in men (P=0.03) with HT. These findings suggest: (i) the frequency of eNOSG894T and/or eNOS4b/a is significantly associated with coronary dysfunction; (ii) eNOS4b/a confers a relatively high risk of hypertension in subjects with atherogenic risk factors; (iii) the frequency of eNOSG894T is high in Fabry hemizygotes with renal complications. Therefore, eNOS gene polymorphism represent a frequent risk factor for vascular abnormalities in CHD, HT and Fabry's disease, afflictions which have in common, the endothelial dysfunction.
authors.affiliation: Institute of Cellular Biology and Pathology "N.Simionescu", Bucharest 050568, Romania. ina.heltianu@icbp.ro
authors.forename: Constantina
authors.initials: C
authors.lastname: Heltianu
authors.forename: Gabriela
authors.initials: G
authors.lastname: Costache
authors.forename: Anca
authors.initials: A
authors.lastname: Gafencu
authors.forename: Miheala
authors.initials: M
authors.lastname: Diaconu
authors.forename: Mihaela
authors.initials: M
authors.lastname: Bodeanu
authors.forename: Carmen
authors.initials: C
authors.lastname: Cristea
authors.forename: K
authors.initials: K
authors.lastname: Azibi
authors.forename: Livia
authors.initials: L
authors.lastname: Poenaru
authors.forename: Maya
authors.initials: M
authors.lastname: Simionescu
mesh_terms: D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000235:genetics*; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A