神经肽Y启动子基因多态性与脑梗死TOAST亚型相关性研究

Association between gene polymorphism of neuropeptide Y promoter and cerebral stroke subtypes according to TOAST criteria

目的 针对脑梗死多因素致病特点，探讨神经肽Y（NPY）启动子基因多态性与脑梗死TOAST分型各亚型的关系。方法采用聚合酶链反应（pcR）和基因测序技术，检测549例脑梗死患者NPY启动子基因-399T／C、-883Tgins／del和-602G／Y基因型及等位基因，其中大动脉粥样硬化型（LAA）190例，小动脉闭塞型（SAO）260例，心源性栓塞型（CE）60例，其他明确原因型（ODE）29例．原因不明型（UE）10例．并与423例汉族健康体检者对照。Logistic回归分析去除混杂因素影响，分析NPY启动子基因多态性与脑梗死TOAST分型各亚型的相关性。结果SAO亚型-399T／C突变基因型CC和等位基因C频率与对照组比较差异均有统计学意义（P=0．046，P=-0．010）；LAA亚型和SAO亚型高尿酸、高血压、心脏病和DM病史较对照组明显增高，比较差异有统计学意义（P〈0．05）：SAO亚型-883Tgins／del缺失突变基因型DD、等位基因D频率与对照组比较差异无统计学意义（P=0．061，P=-0．155）；-399T／C、-883Tgins／del、-602G／T多态性与LAA亚型、CE亚型、0DE亚型和UE亚型患者均无相关性。结论NPY启动子基因-399T／C多态性可能与脑梗死SAO亚型发病存在相关性，高频率等位基因-399C个体可能是SAO亚型重要危险因素。没发现-399T／C、-883Tgins／del、-602G／T基因多态性与LAA亚型、CE亚型、0DE亚型和UE亚型患者有相关性。高尿酸、高血压、心脏病和糖尿病史是LAA亚型和SAO亚型危险因素。

Objective To explore the relationship between gene polymorphism of neuropeptide Y （NPY） promoter and cerebral stroke subtypes according to TOAST （Trail of ORG 10172 in Acute Stroke Treatment） criteria in Chinese Hart population. Methods The gene polymorphisms at position of-399T/C, -883Tgins/del and -602G/T in NPY promoter were detected by PCR method and gene sequencing in 190 cases of large-artery atherosclerosis stroke （LAA）, 260 cases of small-artery occlusion （SAO）, 60 cases of cardioembolism stroke （CE）, 29 cases of stroke of other demonstrated etiology （ODE）, 10 cases of stroke of other undemonstrated etiology （UE） and 423 healthy control subjects. The PCR products were directly sequenced. Multivariate logistic regression was performed to analyze the relationship between gene polymorphism of NPY promoter and cerebral stroke subtypes according to TOAST by removing the confounding variables. Results Significant differences in the f^equency of genotype CC and allele C at position of -399T/C were noted betweer, the patients with SAO and controls （P=-0.046, P=0.010）. Compared with the control group, patients with LAA and SAO were more likely having high level of uric acid, hypertension, diabetes mellitus and heard disease （P〈0.05）. No statistic differences in the frequency of genotype DD and allele D at position of -883Tgins/del were noted between patients with SAO and controls （P=-0.0605, P=-0.155）. Gene polymorphisms of-399T/C, -883Tgins/del and -602G/T did not associate with an increased risk of having LAA, CE, ODE and UE. Conclusions The gene polymorphisms of promoter in position of-399T/C gene maybe associate with the happening of SAO; allele C at the position of-399T/C may raise the risk of the disease. There is no relationship between the gene polymorphisms of promoter at position of-399T/C, -883Tgins/del, -602G/T and the patients with LAA, CE, ODE and UE. High level of uric acid, hypertension, diabetes mellitus and heard disease history are the risk factors of LAA and SAO.