本文選題：CYPC基因多態(tài)性 + 中醫(yī)證型分布��； 參考：《中國中西醫(yī)結(jié)合雜志》2017年03期

【摘要】：目的觀察急性冠脈綜合征(acute coronary syndrome,ACS)患者CYP2C19*2、CYP2C19*3基因多態(tài)性與氯吡格雷抵抗及中醫(yī)證型分布的相關(guān)性。方法 2014年6月—2015年3月采集229例ACS患者的外周血,提取基因組DNA,并進(jìn)行擴(kuò)增及測序,分別進(jìn)行CYP2C19*2、CYP2C19*3基因多態(tài)性與氯吡格雷抵抗及中醫(yī)證型分布的相關(guān)性分析,基因型頻率和等位基因頻率采用基因計數(shù)法及單樣本K-S檢驗,基因型與中醫(yī)證型分布的關(guān)系行Pearson相關(guān)性檢驗。結(jié)果 (1)CYP2C19*2基因多態(tài)性分布:CYP2C19*2(A/A,突變純合子)12例,占總病例數(shù)的5.2%;CYP2C19*2(G/A,雜合子)93例,占總病例數(shù)的40.6%;CYP2C19*2(G/G,正常純合子)124例,占總病例數(shù)的54.2%。突變等位基因頻率為0.255。(2)CYP2C19*3基因多態(tài)性分布:CYP2C19*3(A/A)0例;CYP2C19*3(G/A)26例,占總病例數(shù)的11.4%;CYP2C19*3(G/G)203例,占總病例數(shù)的88.6%。突變等位基因頻率為0.056。(3)CYP2C19基因多態(tài)性與氯吡格雷抵抗的相關(guān)性:CYP2C19*2基因突變純合子較雜合子及正常純合子更易出現(xiàn)氯吡格雷抵抗(R=0.30,P0.01);CYP2C19*3基因雜合子與正常純合子比較,同樣易于出現(xiàn)氯吡格雷抵抗(R=0.34,P0.01)。(4)229例患者中醫(yī)證型分布如下:心血瘀阻證33例(14.41%),氣虛血瘀證51例(22.27%),氣滯血瘀證92例(40.18%),痰阻心脈證17例(7.42%),陰寒凝滯證8例(3.49%),氣陰兩虛證13例(5.68%),心腎陰虛證5例(2.18%),陽氣虛衰證10例(4.37%)。(5)CYP2C19*2基因型與中醫(yī)辨證分型的分布呈顯著相關(guān)(R=0.26,P0.01),突變純合子和大多數(shù)雜合子患者均辨證為氣滯血瘀證。結(jié)論 229例ACS患者CYP2C19基因多態(tài)性與臨床氯吡格雷抵抗關(guān)系密切,其發(fā)生率與CYP2C19*2、CYP2C19*3基因突變頻次相關(guān)。血瘀證(氣滯血瘀證、氣虛血瘀證、心血瘀阻證)為ACS的主要表現(xiàn)證型,且氣滯血瘀證型顯著高于其余證型。CYP2C19*2基因多態(tài)性與中醫(yī)辨證分型相關(guān),氣滯血瘀證患者多數(shù)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.
【作者單位】： 上海中醫(yī)藥大學(xué)附屬曙光醫(yī)院心血管科;
【基金】：國家自然科學(xué)基金資助項目(No.81573647,No.81403137) 上海市科委“科技創(chuàng)新行動計劃”資助項目(No.14401972202);上海市科委項目(No.13ZR1462100)
【分類號】：R541.4

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