CYP2C9-1061A/C基因多态性对特发性房颤患者华法林用量的影响

目的探讨CYP2C9-1601A/C基因多态性在广东地区特发性房颤患者中的分布及其对华法林用量的影响。方法选择广东地区特发性房颤患者150例为病例组,正常人群120例作为对照组,采用PCR-RFLP方法检测CYP2C9基因,比较两组CYP2C9-1601A/C基因型分布特征,并对不同基因型的特发性房颤患者华法林用量进行对比分析。结果 CYP2C9基因1601位A碱基突变为C后,能够被KpnⅠ内切酶识别,产生134 bp和18 bp两个片段。特发性房颤患者中,CYP2C9-1061 AA型105例（70.0%）,AC型40例（26.7%）,CC型5例（3.3%）。AC型比例显著高于正常人群（χ2=13.3259,P=0.0003）,AA型比例显著低于正常人群（χ2=14.5200,P=0.0000）,CC型发生率两组无显著差异（χ2=0.2218,P=0.6377）。AC型及CC型患者华法林用量（3.62±0.58）mg、（3.12±0.16）mg均显著低于AA型的（4.28±0.63）mg（P〈0.01）;CC型患者低于AC型（P〈0.05）。结论广东地区特发性房颤患者中存在较多的CYP2C9 1061A/C基因多态性,并且CYP2C91061A/C突变使患者的华法林用量减低,可作为临床个体化用药的参考。

Effects of CYP2C9-1061A/C gene polymorphism on dosage of warfarin for patients with idiopathic paroxysmal atrial fibrillation

Objective To explore the distribution of CYP2C9-1061A/C gene polymorphism in patients with idiopathic paroxysmal atrial fibrillation in Guangdong area and its effects on the dosage of warfarin. Methods 150 patients with idiopathic atrial paroxysmal fibrillation from Guangdong area were considered as patient group,and 120 healthy people from the same area were regarded as control group. The difference of the distribution of CYP2C9-1061A /C gene polymorphism detected by PCR-RFLP between the 2groups was compared and the difference of dosage of warfarin for the patients with different genotype was analyzed each other. Results The CYP2C9 gene fragment was cut into 134 bp and 18 bp by Kpn Ⅰ enzyme after the A base was mutated by C base. There were 105patients（ 70. 0%） with AA type,40 ones（ 26. 7%） with AC type and 5 ones（ 3. 3%） with CC type. Compared with the normal people,the ratio of AC type in patients with idiopathic paroxysmal atrial fibrillation was higher（ χ2= 13. 3259,P = 0. 0003）,AA ratio was lower（ χ2= 14. 5200,P = 0. 0000）,but CC ratio was not different obviously（ χ2= 0. 2218,P = 0. 6377）. The dosage of warfarin for patients with AC and CC type （ 3. 62 ± 0. 58） mg,（ 3. 12 ± 0. 16） mg] was lower than that with AA type（ 4. 28 ± 0. 63） mg]（ P 〈0. 01）,and the dosage of warfarin for patients with CC type was lower than that with AC type（ P〈0. 05）. Conclusions There are more CYP2C9-1061A /C gene polymorphism in patients with idiopathic paroxysmal atrial fibrillation in Guangdong area. The mutation of CYP2C9-1061A /C decreases the dosage of warfarin. Therefore,CYP2C9 gene polymorphism can be used as reference to the personalized dosage regimen of warfarin in patients with idiopathic atrial paroxysmal fibrillation.