梅州地区TLR4基因连锁不平衡与缺血性脑卒中相关性研究

目的 检测梅州地区缺血性脑卒中患者和健康对照人群TLR4基因的（rs10759932、rs11536879、rs11536891、rs1927914）的基因多态性,经连锁不平衡分析其与缺血性脑卒中的相关性。方法 收集2018年1月1日 - 2018年7月31日住院治疗的突发缺血性脑卒中患者作为病例组,同期在体检中心收集健康人群作为对照组。应用Massarray SNP 分型技术检测两组患者TLR4基因的4个位点基因型,进行Hardy - Weinberg（H - W）平衡检测。采用不同模型分析上述位点不同基因型与脑梗死发病风险的相关性,并通过连锁不平衡分析其与缺血性脑卒中的相关性。结果 病例组纳入病例186名,对照组纳入健康人194名;4种SNP位点均符合H - W 平衡。rs1927914位点G/G基因型在对照组出现频率远远高于病例组（χ2 = 9.267,P＜0.05）。rs10759932位点T/T基因型在女性对照组中出现的频率显著高于男性[OR = 0.38 (0.18 - 0.81),P＜0.05]。4个SNP位点之间均存在连锁不平衡,TGCG基因型组合在缺血性卒中男性患者出现的频率显著高于女性[OR = 3.54 (1.17 - 10.69),P＜0.05]。结论 梅州地区rs1927914位点A＞G为保护性基因突变,可以降低缺血性脑卒中发生。4个位点的连锁不平衡与缺血性脑卒中发生存在部分性别差异,TGCG组合为男性人群的危险基因,脑卒中发生率显著升高。

Association between TLR4 gene linkage disequilibrium and ischemic stroke in Meizhou area

Abstract: Objective The aim of this study was to detect the gene polymorphisms of TLR4 gene (rs10759932, rs11536879, rs11536891, rs1927914) in patients with ischemic stroke and healthy controls in Meizhou area, in order to analyze the correlation between linkage disequilibrium and ischemic stroke. Methods Patients with ischemic stroke hospitalized from January 1,2018 to July 31, 2018, were selected as case group, and healthy people were collected as control group in physical examination department during the same period. Four loci of TLR4 gene were detected by Massarray SNP typing, and Hardy-Weinberg (HW) balance was also calculated. Different models were used to analyze the correlation between different genotypes of the above loci and the risk of ischemic stroke, and the correlation between linkage disequilibrium and ischemic stroke was analyzed. Results 186 cases were included in the case group and 194 healthy persons were included in the control group. The four SNP loci conformed to H-W equilibrium. The frequency of G/G genotype at rs1927914 locus in the control group was much higher than that in the case group (P <0.05). The frequency of T/T genotype at rs10759932 locus in female control group was significantly higher than that in male [OR=0.38 (0.18-0.81)]. Linkage disequilibrium existed among the four SNP loci. The frequency of TGCG genotype combination in male ischemic stroke was significantly higher than that in female [OR=3.54 (1.17-10.69)]. Conclusion rs1927914 locus A>G in Meizhou area was a protective gene mutation, which could reduce the occurrence of ischemic stroke. Linkage imbalance at 4 loci and the occurrence of ischemic stroke had some gender differences. The combination of TGCG was a risk gene in male population, and the incidence of stroke was significantly increased.