Shen Zhi-Jie, Chen Xi-Ao-Kang, Wang Ying-Jie, Guo Wei, Chen Tie-Jun, Wang Xiao-Long
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2017 Mar;37(3):291-296.
Objective To observe correlation between CYP2C19 *2/CYP2C19 *3 gene polymorphism with clopidogrel resistance and distribution of Chinese medicine ( CM) syndrome in acute coronary syndrome (ACS) population. Methods Peripheral blood was collected from 229 ACS patients from June 2014 to March 2015. DNAs were extracted, amplified, and sequenced. Correlations between CYP2C19 *2/CYP2Cl9 *3 gene polymorphisms and clopidogrel resistance/distribution of CM syndrome were analyzed. Gene frequency and allele frequency were tested using gene counting and one-sample K-S test. Correlation between gene types and distribution of CM syndrome was tested by Pearson corre- lation test. Results (1) The CYP2C19 *2 polymorphism distribution: CYP2C19 *2(A/A) (mutant homozygous) 12 cases (5. 2%) ; CYP2C19 * 2 ( G/A ) ( mutant heterozygote ) 93 cases (40. 6%), and CYP2C19 *2 (G/G) (normal homozygous) 124 cases (54. 2%). The mutant allele frequency was 0. 255. (2) The CYP2C19 *3 polymorphism distribution: CYP2C19 *3 (A/A) 0 case (0) ; CYP2C19 *3 (G/A) 26 cases (11. 4%), and CYP2C19 *3 (G/G) 203 cases (88. 6%). The mutant allele frequency was 0. 056. (3) Correlation between CYP2C19 gene polymorphism and clopidogrel resistance: Clopidogrel resistance was more liable to occur in mutant homozygous than in mutant heterozygote and normal homozygous (R =0. 30, P <0. 01). Clopidogrel resistance was more liable to occur in mutant heterozygote than in normal homozygous (R =0. 34, P <0. 01). (4) Among the 229 patients, the CM syndrome distribution were distributed as follows. Blockage of Xin vessels syndrome (BXVS, 33 cases, 14. 41%) ; qi deficiency blood stasis syndrome (QDBSS, 51 cases, 22. 27%) ; qi stagnation blood stasis syndrome (QSBSS, 92 cases, 40.18%) ; phlegm obstructing Xin vessel syndrome (POXVS, 17 cases, 7. 42%) ; yin-cold coag- ulation syndrome (YCCS, 8 cases, 3. 49%) ; qi-yin deficiency syndrome (QYDS, 13 cases, 5.68%) ; Xin-Shen yin deficiency syndrome (XSYDS, 5 cases, 2.18%), yang and qi deficiency syndrome (YQDS, 10 cases, 4. 37%). (5) CYP2C19 *2 gene type was significantly correlated with syndrome typing of CM (R =0. 26, P <0. 01). Mutant homozygous and most mutant heterozygote patients were syndrome typed as QDBSS. Conclusions The polymorphism of CYP2C19 was closely correlated with clopidogrel resist- ance in 229 ACS patients. Its occurrence rate was correlated with CYP2C19 *2/CYP2C19 *3 gene muta- tion frequency. Blood stasis syndrome ( QSBSS, QDBSS, BXVS) were main syndromes of ACS. Be- sides, QSBSS was obviously higher than the rest syndrome types. The polymorphism of CYP2C19 * 2 was correlated with syndrome typing of CM. CYP2C19 *2 gene defect mostly existed in QSBSS.
目的 观察急性冠脉综合征（ACS）人群中CYP2C19 *2/CYP2C19 *3基因多态性与氯吡格雷抵抗及中医证候分布的相关性。方法 收集2014年6月至2015年3月229例ACS患者的外周血。提取DNA、进行扩增及测序。分析CYP2C19 *2/CYP2Cl9 *3基因多态性与氯吡格雷抵抗及中医证候分布的相关性。采用基因计数法和单样本K-S检验检测基因频率和等位基因频率。采用Pearson相关检验检测基因类型与中医证候分布的相关性。结果 （1）CYP2C19 *2基因多态性分布：CYP2C19 *2（A/A）（突变纯合子）12例（5.2%）；CYP2C19 *2（G/A）（突变杂合子）93例（40.6%），CYP2C19 *2（G/G）（正常纯合子）124例（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（0）；CYP2C19 *3（G/A）26例（11.4%），CYP2C19 *3（G/G）203例（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：突变纯合子比突变杂合子和正常纯合子更易发生氯吡格雷抵抗（R =0.30，P <＜0.01）。突变杂合子比正常纯合子更易发生氯吡格雷抵抗（R =0.34，P <0.01）。（4）229例患者中，中医证候分布如下。心血瘀阻证（BXVS，33例，14.41%）；气虚血瘀证（QDBSS，51例，22.27%）；气滞血瘀证（QSBSS，92例，40.18%）；痰阻心脉证（POXVS，17例，7.42%）；寒凝心脉证（YCCS，8例，3.49%）；气阴两虚证（QYDS，13例，5.68%）；心肾阴虚证（XSYDS，5例，2.18%），阳气虚衰证（YQDS，10例，4.37%）。（5）CYP2C19 *2基因类型与中医证型显著相关（R =0.26，P <0.01）。突变纯合子及多数突变杂合子患者证型为气虚血瘀证。结论 229例ACS患者中CYP2C19多态性与氯吡格雷抵抗密切相关。其发生率与CYP2C
