Association Of ENOS Gene Polymorphism With Vascular Cognitive Impairment In Chinese Han Polulation

Objective:Vascular cognitive impairment (VCI) is a complex disorder which occurs due to the combination of several environmental and genetic factors, but, the pathogenesis is still unknown. Studies have reported that the nitric oxide (NO) an important regulatory factor in maintaining vascular homeostasis. NO is produced by vascular endothelial cells, synthesized by endothelial nitric oxide synthase (eNOS). So, the availability of the NO is regulated at the level of eNOS. This study aims to explore the association of eNOS gene polymorphism with VCI.Method:The study group consisted of120VCI patients after cerebral infarct,100cerebral infarct patients with no dementia and100healthy volunteers. The genotypes and allele frequencies of eNOS gene were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP), and gene sequencing methods. And we explored the risk factors to vscular cognitive impairment by analyzing clinical data.Result:1. There were significant differences in genotype distribution and T allele frequency of the894G/T polymorphism among the three groups. Compared to the controls, the VCI and the NoCI patients had a significantly higher frequency of the T allele (19.17%vs8.50%, P=0.001,OR=2.553;19.00%vs8.50%, P=0.002, OR=2.525). However, there was no difference between the VCI patients and the NoCI patients in the frequency of the T allele(19.17%vs19.00%, P=0.965,OR=1.011). In addition, there was no significant difference in the frequency of the a allele among the three groups (x2=2.27, P=0.321).2. There were no significant differences among the three groups in terms of age, gender, smokers, alcoholics, level of education, blood-triglycerides and total cholesterol. However, more VCI patients than controls had diabetes, hypertension, the VCI patients had higher serum low density lipoprotein (LDL) than the other two groups (p<0.05), the serum high density lipoprotein (HDL) was lower than the other two groups (p<0.05).Conclusion:1. Our findings suggest a significant association of the eNOS894G/T polymorphism with ischemic stroke and VCI, T allele may be the susceptibility gene for them. Hence, we speculate that T allele act through associating with ischemic cerebrovascular disease to enhance susceptibility to VCI.2. This study also found some risk factors, such as, hypertension, diabetes, the high level of LDL in plasma. The high level of HDL may be a protective factor. The incidence of VCI can be reduced by preventing and treating the hypertension, diabetes and hyperlipidemia.