| Objective: To study the distribution of clopidogrel resistance related gene polymorphism CYP2C19,PON1,ABCB1 and P2Y12 in the patients of Han population from Yichun area,to provide reference for the individual and reduce the occurrence of cardiovascular adverse events.Methods:We use the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)to detect the genotype of CYP2C19(*2,*3,*17),PON1(Q192R,L55M),ABCB1(C3435T),P2Y12(G52T,C34 T,i-T744C)in 81 patients of Han nationality with coronary heart disease from Yichun area.Through the electronic case system,collect clinical data from the patients who need to take clopidogrel in Yichun People's Hospital from December 2017 to December 2018,analysis of mutant genotype and non-mutant genotype.Results: The frequence of genotype and allele at nine SNP of the patients showed that the frequence of genotype CYP2C19 : CYP2C19*1/*1 had 28 cases(34.6%);CYP2C19*1/*2had 32 cases(39.5%);CYP2C19*1/*3 had 3 cases(39.5%);CYP2C19*2/ 2 had 12 cases(14.8%);CYP2C192/*3 had 6 cases(7.4%).The frequence of allele of CYP2C19:*1 was56.2%,* 2 was 38.3%,* 3 was 5.5%,not find *17 allele;*17 genotype collected in the experiment were all wild homozygote CC type.According to genotype of CYP2C19,fast metabolic CYP2C19*1/*1 has 34.6%,intermediate metabolic CYP2C19*1/*2and CYP2C19*1/*3 has 43.2%;slow metabolic CYP2C19*2/*2 and CYP2C19*2/*3has 22.2%.There was no significant difference in clinical data between genotypes of CYP2C19*2.Clinical data analysis showed that there was a significant difference in D-dimer between CYP2C19*3 gene mutation group and non-mutation group(P<0.05).PON1Q192R genotype frequency: QQ type have 16cases(19.75%);QR type have 45cases(55.56%);RR type have 20 cases(24.69%).PON1L55 M genotype frequency: LL genotype type have 72 cases(88.89%);LM genotype have 6 cases(7.41%);MM genotype have 3 cases(3.7%).Compared with the non-mutation group,the PON1Q192 R gene in the mutation group had a significant difference between the sexes(P<0.05),and the platelet count and triglyceride mutation group were significantly higher than those in the non-mutation group(P<0.05).The hospitalization days of PON1L55 M genotype patients in mutation group were significantly higher than those in non-mutation group(P=0.001),while the platelet count in non-mutation group was higher than that in mutation group(P<0.05).The genotype frequencies of ABCB1C3435 T were 51 cases of CC genotype(62.96%),21 cases of CT genotype(25.93%)and 9 cases of TT genotype(11.11%).The number of scaffolds in ABCB1C3435 T genotype mutation group was significantly higher than that in non-mutation group(P<0.05),and the number of white blood cells in non-mutation group was significantly higher than that in mutation group(P<0.01).The genotype frequence of P2Y12G52 T were: 63 cases of GG genotype,accounting for77.78%;18 cases of GT genotype,accounting for 22.22%;TT genotype was not detected.The genotype frequencies of P2Y12C34 T were: CC 60 cases(74.07%),CT 19 cases(23.46%)and TT 2 cases(2.47%).The genotype frequencies of P2Y12i-T744 C were 69 cases of TT genotype(85.19%),12 cases of CC genotype(14.81%)and CT genotype was not detected.The proportion of drinking in the mutation group of P2Y12G52 T gene was higher than that in the non-mutation group(P<0.05).Compared with the non-mutation group,the number of white blood cells in the mutation group of P2Y12C34 T gene increased significantly(P<0.01).There was no significant difference in clinical data between genotypes of P2Y12i-T744 C.Conclusion:Gender had no significant effect on the distribution of CYP2C19,PON1L55 M,ABCB1C3435T,P2Y12G52 T,P2Y12C34T and P2Y12 i-T744 C gene polym-orphisms in Yichun Han population,but had significant difference in the distribution of PON1Q192 R gene polymorphisms.The distribution of PON1Q192 R gene polymorphism may be related to gender.Patients with one CYP2C19*2 gene in Yichun Han population are advised to take clopidogrel(225mg/d)at three doses,and patients with two CYP2C19*2 genes are advised to take combination drugs or to switch to new antiplatelet drugs such as tegrilol,which are not metabolized by CYP2C19.Patients carrying PON1 Q allele are more likely to develop resistance to clopidogrel.PON1Q192 R gene polymorphism may be associated with clopidogrel resistance.Patients carrying the T allele of ABCB1C3435 T have a higher risk of cardiovascular adverse events.ABCB1C3435 T gene polymorphism may cause clopidogrel resistance.The reduction of platelet aggregation rate in patients with P2Y12C34 T mutant was significantly higher than that in C34 T wild type.The C34 T mutant gene may enhance the inhibition of clopidogrel on platelet aggregation,while the inhibition of platelet aggregation in patients with P2Y12G52 T mutant was significantly lower than that of G52 T wild type,and the effect of clopidogrel on platelet aggregation would be weakened by G52 T mutant.The polymorphisms of P2Y12C34 T and P2Y12G52 T genes may influence the anti-platelet aggregation effect of clopidogrel. |
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