缺血性脑卒中不同证候及表型与WD重复域5B基因多态性的相关性

Association between different syndromes and phenotypes of ischemic stroke and WD repeat domain 5B(WDR5B)gene polymorphism

目的分析缺血性脑卒中(IS)中医证候及临床表型与WD重复域5B(WDR5B)基因rs9843165多态性的关联性。方法收集汉族IS患者样本774例,正常对照样本793例,共计1567例。进行基因检测,使用MassARRAY SNP基因分型实验技术检测WDR5B基因rs9843165多态性位点,并行基因分型。应用非条件Logistic回归模型对疾病和遗传模型的关联进行分析,应用PLINK软件进行基因型与表型的遗传关联分析。结果WDR5B基因rs9843165多态性与IS火热证发生风险的关联性有统计学意义[隐性模型:OR(95%CI)=1.93(1.02~3.67),P=0.044];在校正年龄、性别后,WDR5B基因rs9843165多态性与火热证的发生风险仍有统计学关联[隐性模型:OR_(adj)(95%CI)=1.93(1.01~3.67),P_(adj)=0.046]。WDR5B基因rs9843165多态性与IS患者的D-二聚体(D-D)水平显著相关[加性模型:β(95%CI)=0.28(0.02~0.54),P=0.034;隐性模型:β(95%CI)=0.83(0.26~1.39),P=0.004];WDR5B基因rs9843165多态性与IS患者的极低密度脂蛋白(VLDL)水平[加性模型:β(95%CI)=-0.05(-0.10~0.00),P=0.042]及TG水平[加性模型:β(95%CI)=-0.21(-0.42~0.00),P=0.049]的关联性有统计学意义;WDR5B基因rs9843165多态性与IS患者血浆同型半胱氨酸(Hcy)水平显著相关[加性模型:β(95%CI)=-0.78(-1.38~-0.17),P=0.012;隐性模型:β(95%CI)=-1.83(-3.13~-0.53),P=0.006]。结论WDR5B基因rs9843165多态性可能影响IS火热证的发生,且该位点多态性可能影响IS患者的Hcy、血脂水平及凝血功能。

Objective To explore the association between TCM syndromes and clinical phenotypes of ischemic stroke(IS)and rs9843165 polymorphism of WD repeat domain 5 B(WDR5 B)gene.Methods A total of 774 samples of Han nationality IS patients and 793 normal control samples were collected,for a total of 1567 cases.Genetic testing was performed using MassARRAY SNP genotyping experiment technology to detect the rs9843165 polymorphic locus of WDR5 B gene,and parallel genotyping.The unconditional logistic regression model was used to analyze the association between disease and genetic model,and the PLINK software was used to analyze the genetic association between genotype and phenotype.Results The association between the WDR5 B gene rs9843165 polymorphism and the risk of IS fire-heat syndrome was statistically significant[recessive model:OR(95%CI)=1.93(1.02~3.67),P=0.044].At adjusted age and sex,the WDR5 B gene rs9843165 polymorphism was still statistically associated with the risk of hot syndrome[recessive model:OR_(adj)(95%CI)=1.93(1.01~3.67),P_(adj)=0.046].The WDR5 B gene rs9843165 polymorphism is significantly correlated with DD levels in patients with IS[additive model:β(95%CI)=0.28(0.02~0.54),P=0.034;recessive model:β(95%CI)=0.83(0.26~1.39),P=0.004];WDR5 B gene rs9843165 polymorphism and VLDL level in patients with IS[additive model:β(95%CI)=-0.05(-0.10~0.00),P=0.042]and the level of TG[additive model:β(95%CI)=-0.21(-0.42~0.00),P=0.049]was statistically significant;the rs9843165 polymorphism of the WDR5 B gene and ischemia plasma Hcy levels in stroke patients were significantly correlated[additive model:β(95%CI)=-0.78(-1.38~-0.17),P=0.012;recessive model:β(95%CI)=-1.83(-3.13~-0.53),P=0.006].Conclusions The polymorphism of WDR5 B gene rs9843165 might affect the occurrence of fiery syndrome of IS,and the polymorphism of this locus might affect Hcy,blood lipid level and coagulation function in patients with IS.