Relationship between CYP2C19 and B4GALT2 gene polymorphisms and clopidogrel resistance and prognosis in patients with acute coronary syndrome
Objective To explore the relationship between cytochrome P450 2C19(CYP2C19)and β-1,4-galactosyltrans-ferase 2(B4GALT2)gene polymorphisms and clopidogrel resistance and prognosis in patients with acute coronary syndrome(ACS),aiming to provide a reference for the prognosis assessment of ACS patients.Methods A total of 492 ACS patients admitted to the Huai'an First People's Hospital from June 2019 to October 2022 were selected as the study participants and assigned to a resistance group(n=133)and a non-resistance group(n=359)based on the occurrence of clopidogrel resist-ance.The clinical data,CYP2C19 and B4GALT2 gene polymorphisms of the two groups were compared,and the impact of CYP2C19 and B4GALT2 gene polymorphisms on the prognosis of ACS patients was analyzed.Results Among the 492 ACS patients,133(27.03％)developed clopidogrel resistance.The Adenosine Diphosphate(ADP)inhibition rate in the resist-ance group was lower than in the non-resistance group,and the white blood cell count and neutrophil count were higher than in the non-resistance group,with significant differences(P＜0.05).No significant differences were noted in age,gender composition,body mass index,comorbidities,and laboratory examination indicators between the two groups(P＞0.05).The frequency distribution of CYP2C19 rs4244285,CYP2C19 rs4986893,and B4GALT2 rs1061781 gene frequencies in pa-tients of the resistance and non-resistance groups was representative of the population,with no statistically significant differ-ences(P＞0.05).The frequency of allele A at the CYP2C19 rs4244285 site,allele A at the CYP2C19 rs4986893 site,and allele C at the B4GALT2 rs1061781 site in the resistance group was significantly higher than in the non-resistance group(P＜0.05).The incidence of major adverse cardiovascular events(MACE)in the resistance group was significantly higher than that in the non-resistance group[33.08％(44/133)vs.22.28％(80/359);x2=6.003,P=0.014].The frequency of allele A at the CYP2C19 rs4244285 site and allele C at the B4GALT2 rs1061781 site in patients with poor prognosis was sig-nificantly higher than in those with good prognosis(P＜0.05).No significant difference was found in the gene frequency at the CYP2C19 rs4986893 site among patients with different prognoses(P＞0.05).COX regression analysis results showed that age＞74 years(HR=1.686,95％CI:1.163--2.443),body mass index＞25 kg/m2(HR=1.647,95％CI:1.110～2.444),diabetes(HR=1.570,95％CI:1.091～2.259),CYP2C19 rs4244285 AA genotype(HR=1.642,95％CI:1.133～2.379),and B4GALT2 rs1061781 CC genotype(HR=1.738,95％CI:1.026～2.943)are independent risk fac-tors for the prognosis of ACS patients(P＜0.05).The cumulative survival probabilities of ACS patients with different CYP2C19 rs4244285 and B4GALT2 rs1061781 genotypes were compared,and the differences were statistically significant(log rank x2=25.920,5.292,both P＜0.05).Conclusion The AA genotype at the CYP2C19 rs4244285 site and the CC genotype at the B4GALT2 rs1061781 site are associated with clopidogrel resistance in ACS patients and can be used for risk assessment of poor prognosis in these patients.
万方数据
维普
