229例急性冠脉综合征氯吡格雷抵抗患者CYP2C19基因多态性与中医证型分布的相关性

发布时间：2018-05-01 20:49

本文选题：CYPC基因多态性 + 中医证型分布　；参考：《中国中西医结合杂志》2017年03期

【摘要】：目的观察急性冠脉综合征(acute coronary syndrome,ACS)患者CYP2C19*2、CYP2C19*3基因多态性与氯吡格雷抵抗及中医证型分布的相关性。方法 2014年6月—2015年3月采集229例ACS患者的外周血,提取基因组DNA,并进行扩增及测序,分别进行CYP2C19*2、CYP2C19*3基因多态性与氯吡格雷抵抗及中医证型分布的相关性分析,基因型频率和等位基因频率采用基因计数法及单样本K-S检验,基因型与中医证型分布的关系行Pearson相关性检验。结果 (1)CYP2C19*2基因多态性分布:CYP2C19*2(A/A,突变纯合子)12例,占总病例数的5.2%;CYP2C19*2(G/A,杂合子)93例,占总病例数的40.6%;CYP2C19*2(G/G,正常纯合子)124例,占总病例数的54.2%。突变等位基因频率为0.255。(2)CYP2C19*3基因多态性分布:CYP2C19*3(A/A)0例;CYP2C19*3(G/A)26例,占总病例数的11.4%;CYP2C19*3(G/G)203例,占总病例数的88.6%。突变等位基因频率为0.056。(3)CYP2C19基因多态性与氯吡格雷抵抗的相关性:CYP2C19*2基因突变纯合子较杂合子及正常纯合子更易出现氯吡格雷抵抗(R=0.30,P0.01);CYP2C19*3基因杂合子与正常纯合子比较,同样易于出现氯吡格雷抵抗(R=0.34,P0.01)。(4)229例患者中医证型分布如下:心血瘀阻证33例(14.41%),气虚血瘀证51例(22.27%),气滞血瘀证92例(40.18%),痰阻心脉证17例(7.42%),阴寒凝滞证8例(3.49%),气阴两虚证13例(5.68%),心肾阴虚证5例(2.18%),阳气虚衰证10例(4.37%)。(5)CYP2C19*2基因型与中医辨证分型的分布呈显著相关(R=0.26,P0.01),突变纯合子和大多数杂合子患者均辨证为气滞血瘀证。结论 229例ACS患者CYP2C19基因多态性与临床氯吡格雷抵抗关系密切,其发生率与CYP2C19*2、CYP2C19*3基因突变频次相关。血瘀证(气滞血瘀证、气虚血瘀证、心血瘀阻证)为ACS的主要表现证型,且气滞血瘀证型显著高于其余证型。CYP2C19*2基因多态性与中医辨证分型相关,气滞血瘀证患者多数存在CYP2C19*2基因缺陷。
[Abstract]:Objective to investigate the association of CYP2C192C193gene polymorphism with clopidogrel resistance and distribution of TCM syndromes in patients with acute coronary syndrome (ACS). Methods Peripheral blood samples were collected from 229 patients with ACS from June 2014 to March 2015. Genomic DNA was extracted, amplified and sequenced. The relationship between CYP2C19C192CYP2C193 gene polymorphism and clopidogrel resistance and distribution of TCM syndromes was analyzed. Genotype frequency and allelic frequency were detected by gene counting method and single sample K-S test. The relationship between genotype and distribution of TCM syndromes was tested by Pearson correlation test. Results the polymorphism distribution of CYP2C19-2 gene was: CYP2C192G / A, 12 cases of homozygote, accounting for 5.2% of total cases, 93 cases of heterozygote, 40.6% of total cases, 124 cases of normal homozygote, accounting for 54.2% of the total number of cases. The frequency of mutation alleles was 0.255.(2)CYP2C19*3 gene polymorphism. There were 26 cases of CYP2C19 / 3G / A, accounting for 11.4% of the total number of cases, accounting for 88.6% of the total number of cases. The frequency of mutation allele is 0.056.(3)CYP2C19 gene polymorphism and clopidogrel resistance. The homozygote of CYP2C19k2 gene is more likely to present clopidogrel resistance gene heterozygote than heterozygote and normal homozygote, and the heterozygote of CYP2C193 gene is more likely to appear than that of normal homozygote. Similarly, clopidogrel resistance to RP0. 34N P0. 01P0. 01P0. 01C. The distribution of TCM syndromes is as follows: 33 patients with heart blood stasis syndrome, 51 patients with qi deficiency and blood stasis syndrome, 92 patients with qi stagnation and blood stasis syndrome, 92 patients with Qi stagnation and blood stasis syndrome, 17 patients with phlegm blocking heart and vein syndrome, 17 patients with phlegm blocking heart vein syndrome, 8 patients with cold stagnation of Yin syndrome, 8 patients with cold stagnation syndrome and 3. 49A syndrome with deficiency of qi and yin. There was a significant correlation between the distribution of CYP2C19F2 genotype and TCM syndrome. The syndrome of deficiency of qi and blood stasis was found in the mutant homozygote and most of heterozygotes. The results showed that there was a significant correlation between the genotype of CYP2C19F2 and the distribution of TCM syndrome differentiation in 13 cases (P = 5.68), 5 cases of deficiency of Heart and Kidney Yin (n = 5), and 10 cases of deficiency of Yang Qi (n = 10) were identified as stagnation of Qi and Blood stasis. Conclusion the polymorphism of CYP2C19 gene is closely related to clopidogrel resistance in 229 patients with ACS. The incidence of clopidogrel resistance is associated with the mutation frequency of CYP2C19cogene. Blood stasis syndrome (Qi stagnation and blood stasis syndrome, qi deficiency and blood stasis syndrome, heart blood stasis syndrome) is the main manifestation of ACS, and the polymorphism of qi stagnation and blood stasis syndrome is significantly higher than that of other syndrome types. Most patients with Qi stagnation and Blood stasis syndrome have CYP2C19*2 gene defects.
【作者单位】：上海中医药大学附属曙光医院心血管科;
【基金】：国家自然科学基金资助项目(No.81573647,No.81403137) 上海市科委“科技创新行动计划”资助项目(No.14401972202);上海市科委项目(No.13ZR1462100)
【分类号】：R541.4

【相似文献】