CYP2C19基因多态性与脑梗死患者脑血管储备和神经炎症水平的相关性

Correlation between CYP2C19 gene polymorphism and cerebral vascular reserve and neuroinflammation level in patients with cerebral infarction

目的探究CYP2C19基因多态性与脑梗死患者脑血管储备和神经炎症水平的相关性。方法回顾性选取2019年2月至2021年11月铜仁市人民医院收治的脑梗死患者90例为脑梗死组,另选取在铜仁市人民医院体检中心年龄和性别比例相匹配的90名健康者为对照组。通过酶联免疫吸附试验测定血清神经炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和超敏C反应蛋白(hs-CRP)]的水平。通过氙气计算机断层扫描(Xe-CT)测量受试者的脑血流量(CBF)和脑血管储备能力(CRC)。采用实时荧光定量PCR检测CYP2C19基因型。进行Cox回归分析以研究神经炎症因子水平和脑血管储备是否与CYP2C19基因多态性独立相关性。结果脑梗死组神经炎症因子IL-6、TNF-α和hs-CRP水平较对照组升高,CBF和CRC较对照组降低,差异均有统计学意义(P<0.05)。脑梗死组AA基因型频率较对照组降低,AG基因型频率和GG基因型频率较对照组升高,差异均有统计学意义(P<0.05)。脑梗死组A等位基因频率较对照组降低,而G等位基因频率较对照组升高,差异有统计学意义(P<0.05)。GG基因型脑梗死患者中神经炎症因子IL-6、TNF-α和hs-CRP水平较AG和AA基因型脑梗死患者显著升高,G等位基因的脑梗死患者IL-6、TNF-α和hs-CRP水平较A等位基因的脑梗死患者升高,差异均有统计学意义(P<0.05)。GG基因型脑梗死患者CBF和CR较AG和AA基因型脑梗死患者降低,G等位基因的脑梗死患者CBF和CR较A等位基因的脑梗死患者降低,差异均有统计学意义(P<0.05)。结论脑梗死患者中CYP2C19*2(SNP 681G>A)多态性与神经炎症升高和脑血管储备降低相关,CYP2C19可能是脑梗死疾病的候选基因。

Objective To explore the relationship between CYP2C19 gene polymorphism and cerebral vascular reserve and neuroinflammation levels in patients with cerebral infarction.Methods Ninety patients with cerebral infarction admitted to Tongren People's Hospital from February 2019 to November 2021 were retrospectively selected as the cerebral infarction group.In addition,90 healthy volunteers with matching age and sex ratio were recruited as the control group in the physical examination center of Tongren People's Hospital.The levels of serum neuroinflammatory factors[interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α),and high-sensitivity C-reactive protein(hs-CRP)]were detected by enzyme-linked immunosorbent assay.The subjects'cerebral blood flow(CBF)and cerebrovascular reserve capacity(CRC)were measured by Xenon computed tomography(Xe-CT).PCRCYP2C19 genotypes were detected using real-time fluorescence quantification.Cox regression analysis was performed to investigate whether the levels of neuroinflammatory factors and cerebrovascular reserve were independently correlated with CYP2C19 polymorphism.Results There was no difference in general information between the two groups of subjects(P>0.05).The levels of neuroinflammatory factors IL-6,TNF-αand hs-CRP in the cerebral infarction group were higher than those in the control group,and the CBF and CRC in the cerebral infarction group were lower than those in the control group,the differences were statistically significant(P<0.05).The frequency of AA genotype in the cerebral infarction group was lower than that in the control group,and the frequency of AG genotype and GG genotype in the cerebral infarction group were higher than that in the control group,the differences were statistically significant(P<0.05).The frequency of A allele in the cerebral infarction group was lower than that in the control group,while the frequency of G allele was higher than that in the control group,the differences were statistically significant(P<0.05).The levels of neuroinflammatory factors IL-6,TNF-αand hs-CRP in patients with GG genotype cerebral infarction were significantly higher than those in patients with AG and AA genotype cerebral infarction,the levels of IL-6,TNF-αand hs-CRP in patients with cerebral infarction of G allele were higher than those of A allele patients with cerebral infarction,the differences were statistically significant(P<0.05).CBF and CR in patients with GG genotype cerebral infarction were lower than those with AG and AA genotype cerebral infarction,CBF and CR in patients with G allele cerebral infarction were lower than those with A allele cerebral infarction,the differences were statistically significant(P<0.05)).Conclusion CYP2C19*2(SNP 681G>A)polymorphism in patients with cerebral infarction is associated with increased neuroinflammation and decreased cerebrovascular reserve.The existence of these correlations indicates that CYP2C19 may be a candidate gene for cerebral infarction disease.