Relation between ABCB1 gene rs1045642 polymorphism and clopidogrel resistance in Han patients with ischemic stroke at different ages

Hu Pan; He Zhiyi

doi:10.3760/j.issn.1673-4777.2018.09.010

Abstract：Objective To investigate the relation between polymorphism of ABCB1 gene rs1045642 and clopidogrel resistance(CR) in Han patients with ischemic stroke at different ages.Methods From March 2015 to June 2017,62 ischemic stroke patients with CR admitted to the First Affiliated Hospital of China Medical University were selected as CR group;62 ischemic stroke patients without CR were matched as NCR group.Immunological and serological risk factors were analyzed through Logistic regression.Frequency and allelic variation of ABCB1 gene rs1045642 genotype were detected in all patients and analyzed among different ages.The correlation between different genotypes and serum inflammatory factors was analyzed through Pearson test.Results Multivariate Logistic regression showed that interleukin-1 (IL-1,odds ratio =3.35,95％ confidence interval:2.65-4.31),tumor necrosis factor-α (TNF-α,odds ratio =1.56,95％ confidence interval:0.38-4.36) and high-sensitivity C-reactive protein (hs-CRP,odds ratio =3.42,95％ confidence interval:1.21-7.74) were independent risk factors of CR in patients with ischemic stroke (all P ＜ 0.05).In the CR and NCR groups,the single nucleotide polymorphism rs1045642 of ABCB1 gene was found to be C/C,T/T and C/T.The frequency of T/T genotype in the CR group was significantly higher than that in the NCR group(41.94％ vs 11.29％);the frequency ofT allele in the CR group was significantly higher than that in the NCR group (54.84％ vs 33.06％) (both P ＜ 0.01).In the CR group,the frequency of T/T genotype in patients ≥ 60 years old was significantly higher than that in patients ＜60 years old(54.55％ vs 27.59％);the C allele decreased and T allele increased with age(all P ＜0.05).Serum levels of IL-1 (r =0.541,P =0.032),TNF-α (r =0.699,P =0.014) and hs-CRP (r =0.921,P ＜ 0.001) in the T/T genotype were significantly higher than in the C/C and C/T genotype and they were positively correlated with age.Conclusions Elderly patients with ischemic stroke are more susceptible to CR in the rs1045642T/T genotype.Elevation of serum IL-1,TNF-α and hs-CRP may be an immunological mechanism of CR.