Endothelial nitric oxide synthase gene polymorphisms and the risk of silent brain infarction

被引:37
作者
Song, Jihwan [3 ]
Kim, Ok Joon [2 ]
Kim, Hyun Sook [2 ]
Bae, Su Jin [1 ]
Hong, Sun Pyo [4 ]
Oh, Doyeun [1 ]
Kim, Nam Keun [1 ]
机构
[1] CHA Univ, Inst Clin Res, Sch Med, Bundang CHA Gen Hosp, Songnam 463712, South Korea
[2] CHA Univ, Dept Neurol, Sch Med, Bundang CHA Gen Hosp, Songnam 463712, South Korea
[3] CHA Univ, CHA Stem Cell Inst, Sch Med, Seoul 135081, South Korea
[4] Genematrix Inc, Yongin 449913, South Korea
关键词
endothelial nitric oxide synthase; silent brain infarction; polymorphism; haplotype; risk factors; WHITE-MATTER LESIONS; CEREBROVASCULAR-DISEASE; STROKE PATIENTS; PREVALENCE; POPULATION; HYPERHOMOCYSTEINEMIA; GLU298ASP; SMOKING; G894T;
D O I
10.3892/ijmm_00000410
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Silent brain infarction (SBI), a unique cerebrovascular disorder, is frequently detected on magnetic resonance imaging (MRI) of apparently healthy elderly persons, and it is known to increase the risk of stroke and other related diseases. Although detailed mechanisms of SBI pathogenesis have yet to be determined, recent studies suggest that SBI is significantly influenced by genetic factors. In this study, we investigated polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (i.e., -786T>C, 4a4b and 894G>T) as possible risk factors for SBI. We enrolled 269 patients with SBI and 234 control subjects and examined their fasting plasma homocysteine and folate levels, and analyzed for eNOS polymorphisms and haplotypes. The prevalence of SBI was shown to be significantly higher in patients with the eNOS 894GT genotype (OR, 2.00; 95% CI, 1.30-3.08) and 894GT+TT genotype (OR, 2.05; 95% CI, 1.34-3.16), compared with the 894GG genotype. However, in the case of -786T>C and 4a4b polymorphisms, no significant difference was observed between SBI patients and normal subjects. Interestingly, we found that the prevalence of SBI can increase twice as high when either -786T>C or 4a4b polymorphism was combined with 894G>T polymorphism, -786TC+CC/ 894GT+TT (OR, 3.83; 95% CI, 1.24-11.80) and 4a4b+4a4a/894GT+TT (OR, 4.08; 95% CI, 1.34-12.40), respectively. According to haplotype analysis, we found that three haplotypes (-786T-4b-894G, -786T-4b-894T and -786C-4a-894T) were shown to be significantly different between SBI patients and control subjects. These results indicate that eNOS polymorphisms and haplotypes serve as risk factors for SBI, and three different polymorphic loci in the eNOS gene play interactively, thereby leading to synergistic effects for the generation of SBI.
引用
收藏
页码:819 / 823
页数:5
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