The Relation Between Endothelial Nitric Oxide Synthase Gene Polymorphisms And Atherosclerosis Diseases

Objective:Nitric oxide (NO) from the endothelium, produced by oxidation of L-arginine to L-citruline for the action at the endothelial nitric oxide synthase (eNOS) is considered an important atheroprotective factor. The 4b/a, G894T and T786C polymorphic variants of the eNOS gene have been implicated in the development of artherosclerosis diseases such as coronary heart disease (CHD) or carotid atherosclerosis (CAS). We investigated the relation between occurrence and development of CHD or CAS and the 4b/a, G894T and T786C polymorphisms of the eNOS gene in a Tianjin Han population.Methods:Nine hundred and seven patients undergone coronary angiography in Tianjin Chest hospital cardiovascular department from April 2007 to October 2008 were enrolled in the study. The blood samples and complete clinical information were collected. The eNOS gene polymorphisms were analyzed by polymerase chain reaction (PCR) or polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Meanwhile some of the patients were undergone B-mode ultrasonography and the corresponding data was collected. We studied the relation between the eNOS gene polymorphisms and CHD in the 545 subjects whose three gene polymorphisms were successively determined, of whom 266 had CHD confirmed by coronary angiography and 279 were controls. The 392 subjects undergone B-mode ultrasonography among them were classified into the CAS group and control group according to the assay results, and in which we investigate the association of the eNOS gene polymorphisms and CAS, and the relation between the eNOS gene polymorphisms and the distribution, Crouse score and total square of CAS plaques.Results:1. The 4b/a polymorphism of eNOS gene was not found to be significantly associated with risk of CHD or CAS (P=0.010); in addition, it is not associated with the distribution of affected vessel and Gensini scores.2. After adjustment for gender and age, the relations between CHD and genotype GT or (GT+TT) (OR= 1.62, 95%CI=(1.01,2.61), P=0.046; OR=1.60,95%CI=(1.01.2.53), P=0.043, respectively), or the relations between CAS and genotype (GT+TT) and allele T (OR=1.73, 95%CI=(1.03.2.92). P=0.040; OR=1.70,95%CI=(1.08.2.69),P=0.023, respectively), were all statistically significant. But after adjusted for other risk factors, the relations were no longer found. The affected vessel distribution was significantly different between subjects with genotype (GT+TT) and GG.3. After adjustment for gender and age, we found the relations between the genotype TC and (TC+CC) with he occurrence of CHD were all with statistical trend (P=0.075, P=0.080), but did not find any relation between T786C polymorphism and CAS. There was significant difference in the Gensini score and affected vessel distribution between genotype (TC+CC) and TT (P=0.038, P=0.006).4. No significant relations were found between these eNOS gene polymorphisms and the carotid atherosclerosis plaques distribution, the Crouse scores and the total square of the plaques.5. Using Logistic regression with adjustment for all common risk factors, the haplotype 4b-G-C was significantly associated with CHD and CAS (OR=5.62,95%CI=(1.17,27.0), P=0.032; OR=4.23,95%CI=(1.18,15.1),P=0.027), and the relation between haplotype 4b-T-T and CAS was close to statistical significance (OR=1.89,95%CI=(0.98,3.64), P=0.057).Conclusions:In the studied Tianjin Han population,1. The eNOS gene 4b/a polymorphism is not a genetic risk factor for CHD or CAS; the G894T polymorphism is a genetic risk factor for CHD or CAS, but is not an independent risk factor. The relation between T786C polymorphism and CHD is with statistical trend, while it is not associated with the presence of CAS.2. The eNOS gene polymorphisms G894T and T786C are all associated with the extent of affected coronary artery, with the T786C polymorphism also associated with the severity of atherosclerosis. However, none of the polymorphisms was in relation with the distribution, extent and severity of the carotid atherosclerosis plaques.3. There are many common independent risk factors for CHD and CAS, such as age, male, smoking, diabetes mellitus and dyslipidemia, and the haplotype 4b-G-C seems to be an common independent risk factor for CAD and CAS, and it is potentially involved in the atherogenic pathway.