TLR9 基因及-1237T/C 位点多态性与心血管疾病关联研究

目的：通过生物信息学分析 Toll 样受体 9（ toll-like receptor 9,TLR9） 基因及检测 -1237T/C 位点多态性,探究TLR9 基因与心血管疾病的关联性。方法：利用生物信息学方法对TLR9 进行理化性质、单核苷酸多态性 （single nucleotide polymorphism,SNP）位点、关联基因互作和GO 功能注释等分析。提取189 份血浆标本外周血基因组DNA（包括心血管疾病组68 例,健康对照组121 例）,经基因扩增后对扩增产物进行酶切、分型、测序,并统计分析与心血管疾病的相关性。结果：TLR9为亲水性碱性蛋白质,有4 个核定位信号和多个潜在的线性B 细胞表位,其编码蛋白的二级结构以α螺旋为主。TLR9 作为中心节点蛋白,与MYD88、TBK1 和CD40 等10 个蛋白发生互作,且主要富集在Toll 样受体信号通路和炎症反应等信号通路。TT 和TC 基因型分布频率在健康对照组中分别为71.90% 和28.10%,在疾病组分别为47.06% 和52.94%,两组比较有统计学意义,心血管疾病患者TC 基因型分布频率增高。结论：TLR9 基因及其-1237T/C 多态性与心血管疾病关系紧密。

Association Study of TLR9 Gene and Its Polymorphism at -1237T / C Site with Cardiovascular Disease

Objective：To explore the relationship between toll-like receptor 9 （TLR9） gene and cardiovascular disease by bioinformatics analysis of TLR9 gene and its -1237t / C polymorphism. Methods：The physical and chemical properties,single nucleotide polymorphism（SNP） sites,associated gene interaction and GO function annotation of TLR9 were analyzed by bioinformatics.The genomic DNA of peripheral blood was extracted from 189 plasma samples （including 68patients with cardiovascular disease and 121 healthy controls）. After gene amplification,the amplified products were digested,typed and sequenced,the correlation with cardiovascular disease was statistically calculated. Results：TLR9 is a hydrophilic basic protein with four nuclear localization signals and several potential linear B cell epitopes. The secondary structure of the protein is mainly α helix. As a hub protein,TLR9 interacts with 10 proteins such as MYD88,TBK1 and CD40,and is mainly enriched in Toll-like receptor signal pathway and inflammatory response signal pathway. The distribution frequencies of TT and TC genotypes were 71.90% and 28.10% in the healthy control group,47.06% and 52.94% in the disease group,respectively. There was statistical significance between the two groups. Conclusion：TLR9 gene and its 1237T / C polymorphism are closely related to cardiovascular diseases.