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目的探讨中国南方汉族人Toll样受体4基因(TLR4)多态性rs1927914、rs10759932和rs11536889与中风证型(风痰瘀阻证、气虚血瘀证)易感性、基因表达水平、细胞因子及血脂代谢的相关性。方法采用病例对照研究方法,将559例中风患者按中医辨证分气虚血瘀型组(248例)及风痰瘀阻型组(311例),另设一性别、年龄相匹配健康对照组(605例)。所有研究对象均来自汉族。采用Sequenom Mass ARRAY技术对TLR4基因的rs1927914、rs10759932和rs11536889进行基因分型检测,实时荧光定量PCR(qPCR)检测TLR4信使核糖核酸(mRNA)表达水平,酶联免疫吸附测定(ELISA)检测白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-12(IL-12)、肿瘤坏死因子-α(TNF-α)水平,HITACHI日立7600全自动生化分析仪测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)水平。结果 rs10759932的等位基因频率在中风气虚血瘀型男性病例与男性对照组之间的分布存在统计学差异(P<0.05)。rs1927914(显性模型:OR=0.65,95%CI=0.43-0.96,Padj=0.031)、rs10759932(显性模型:OR=0.64,95%CI=0.41-0.99,Padj=0.046)位点多态性与男性中风气虚血瘀证易感性显著关联。携带rs10759932位点TT基因型的中风气虚血瘀型患者的IL-8血清水平显著低于CC+CT者(P<0.01)。rs11536889多态性与中风气虚血瘀型男性患者的TG水平(加性模型:Padj=0.021,显性模型:Padj=0.013)、HDL(显性模型:Padj=0.032)显著关联。结论 TLR4基因多态性影响汉族男性中风气虚血瘀证的发生及炎性反应和血脂代谢病理过程。
Objective To investigate the association between polymorphisms of Toll-like receptor 4 (TLR4) rs1927914, rs10759932 and rs11536889 and susceptibility to stroke syndrome (wind phlegm and stasis syndrome, qi deficiency and blood stasis syndrome), gene expression, cytokines and lipids Metabolic relevance. Methods A case-control study was conducted in 559 stroke patients according to syndrome differentiation of Qi and blood stasis type (248 cases) and wind phlegm and stasis type group (311 cases). Another sex-matched age-matched healthy control group (605 example). All subjects were from Han nationality. The genotypes of rs1927914, rs10759932 and rs11536889 of TLR4 gene were detected by Sequenom Mass ARRAY. The expression of TLR4 messenger RNA (mRNA) was detected by real-time quantitative PCR (qPCR). The levels of interleukin IL-1β, IL-6, IL-8, IL-12, TNF-α ), HITACHI 7600 automatic biochemical analyzer was used to determine the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) Results The frequency of allele rs10759932 was significantly different between male and female controls (P <0.05). rs1927914 (dominant model: OR = 0.65, 95% CI = 0.43-0.96, Padj = 0.031), rs10759932 (dominant model: OR = 0.64, 95% CI = 0.41-0.99, Padj = 0.046) Significantly associated with susceptibility to male stroke with deficiency of blood stasis. Serum levels of IL-8 in patients with stroke-Qi deficiency and blood stasis syndrome carrying rs10759932 TT genotype were significantly lower than those in CC + CT patients (P <0.01). rs11536889 polymorphism was significantly associated with TG levels (additive model: Padj = 0.021, dominance model: Padj = 0.013) and HDL (dominance model: Padj = 0.032) in male patients with stroke-Qi deficiency and blood stasis type. Conclusion TLR4 gene polymorphism affects the occurrence and inflammatory reaction and the pathological process of blood lipid metabolism in the Han men with stroke-Qi deficiency and blood-stasis syndrome.