Department of Emergency, Weihai Municipal Hospital, Shandong University, Weihai, China.
Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6873-6880. doi: 10.26355/eurrev_202006_21677.
To explore the correlation between angiotensin II type 1 receptor (AT1R) gene polymorphism and epilepsy secondary to cerebral infarction and its significance for the diagnosis of this disease.
A total of 200 patients with epilepsy secondary to cerebral infarction were enrolled from our hospital as observation group, and 200 patients without epilepsy after cerebral infarction as control group. Genomic deoxyribonucleic acids (DNAs) were extracted from the peripheral blood of the subjects, and the polymorphic regions at AT1R gene loci rs380400, rs1799870, rs12721273, and rs55707609 were amplified via polymerase chain reaction (PCR) and sent to the company for sequencing. The concentration of farnesyl diphosphate synthase (FDPS) was determined using enzyme-linked immunosorbent assay (ELISA) kit, and activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured in the Laboratory Department.
There were no differences in the allele distributions at AT1R gene loci rs380400 (p=0.070), rs179987 (p=0.0.280), and rs55707609 (p=0.046), but in the allele distribution at rs12721273 (p=0.001) between control group and observation group, and observation group exhibited a significantly lower frequency of allele G in cerebral infarction patients than control group [153 (0.383) vs. 198 (0.495)]. The frequency of genotype GT at rs12721273 was lower [71 (0.355)] and that of genotype TT was evidently higher [88 (0.440)] in observation group (p=0.000). Control group showed a notably lower frequency of genotype AA [47 (0.235)] and a markedly higher frequency of genotype AT [110 (0.550)] at rs55707609 (p=0.000). Observation group exhibited a substantially lower frequency of recessive model AG+GG [128 (0.640)] (p=0.037), and a notably higher frequency of homozygous model AA [72 (0.360)] (p=0.048) at AT1R gene locus rs380400, a remarkably lower frequency of dominant model GG+GT [112 (0.560)] (p=0.002) at rs12721273, and a significantly lower frequency of recessive model AT+TT [126 (0.630)] (p=0.000) and a considerably lower frequency of heterozygous model AT [84 (0.420)] (p=0.026) at rs55707609. The frequencies of AT1R gene haplotypes ACGA (p=0.001), ACGT (p=0.045), ACTT (p=0.000), ATTT (p=0.048), GCTA (p=0.000), and GTGA (p=0.005) in observation group were distinctly higher than those in control group, and the frequencies of the haplotypes ACTA (p=0.000) and ATTA (p=0.029) were evidently lower than those in control group. The loci rs12721273 and rs1799870 showed a significant association (D'=0.783), and APTT was considerably correlated with genotype AG at rs380400 (p=0.042), PT with genotype CC at rs1799870 (p=0.002) and FDPS with genotype AA at rs55707609 (p=0.015).
The polymorphisms of AT1R gene loci rs380400, rs1799870, rs12721273, and rs55707609 are correlated with the susceptibility to epilepsy secondary to cerebral infarction.
探讨血管紧张素Ⅱ 1 型受体（AT1R）基因多态性与脑梗死继发癫痫的相关性及其对该病诊断的意义。
选取我院 200 例脑梗死继发癫痫患者作为观察组，同期 200 例无脑梗死癫痫患者作为对照组。采用聚合酶链反应（PCR）扩增外周血基因组脱氧核糖核酸（DNA），并对 AT1R 基因 rs380400、rs1799870、rs12721273 和 rs55707609 多态性区域进行测序。采用酶联免疫吸附试验（ELISA）试剂盒测定法呢基二磷酸合酶（FDPS）浓度，检验科测定活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）。
对照组与观察组 AT1R 基因 rs380400（p=0.070）、rs179987（p=0.028）和 rs55707609（p=0.046）的等位基因分布无差异，但 rs12721273（p=0.001）的等位基因分布有差异，观察组脑梗死患者的等位基因 G 频率明显低于对照组[153（0.383）比 198（0.495）]。观察组 rs12721273 基因型 GT 的频率较低[71（0.355）]，TT 基因型的频率明显较高[88（0.440）]（p=0.000）。对照组 rs55707609 基因型 AA 的频率明显较低[47（0.235）]，AT 基因型的频率明显较高[110（0.550）]（p=0.000）。观察组 rs380400 基因的隐性模型 AG+GG 的频率明显较低[128（0.640）]（p=0.037），AA 基因型的频率明显较高[72（0.360）]（p=0.048）；rs12721273 的显性模型 GG+GT 的频率明显较低[112（0.560）]（p=0.002），rs55707609 的隐性模型 AT+TT 的频率明显较低[126（0.630）]（p=0.000），杂合子 AT 基因型的频率明显较低[84（0.420）]（p=0.026）。观察组 AT1R 基因单倍型 ACGA（p=0.001）、ACGT（p=0.045）、ACCT（p=0.000）、ATTT（p=0.048）、GCTA（p=0.000）和 GTGA（p=0.005）的频率明显高于对照组，ACTA（p=0.000）和 ATTA（p=0.029）的频率明显低于对照组。rs12721273 和 rs1799870 位点有显著相关性（D'=0.783），APTT 与 rs380400 基因的 AG 基因型显著相关（p=0.042），PT 与 rs1799870 基因的 CC 基因型显著相关（p=0.002），FDPS 与 rs55707609 基因的 AA 基因型显著相关（p=0.015）。
AT1R 基因 rs380400、rs1799870、rs12721273 和 rs55707609 多态性与脑梗死继发癫痫的易感性有关。
