Association between genetic polymorphisms of cytochrome P450 2C19 and the risk of cerebral ischemic stroke in Chinese

Abstract

BackgroundCytochrome P450 (CYP) 2C19 is a very important drug metabolizing enzyme. Although the single nucleotide polymorphisms (SNPs) of CYP2C19 G681A and G636A have been suggested that they may increase the incidence of cardiovascular events, the relationship between SNPs in CYP2C19 and cerebral ischemic stroke (CIS) are unclear. The aim of this study was to investigate the correlation between the distribution of G681A and G636A polymorphisms in CYP2C19 gene and the risk of CIS in Chinese.MethodsThe peripheral blood DNA was extracted from 299 patients with CIS and 295 healthy controls. The genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism. The sampled sequencing was applied to verify the correctness of genotyping results. Both the genotype and allele distributions were compared in patients with CIS and healthy controls.ResultsThe frequencies of CYP2C19 681AA (11.7% vs. 2.7%; P = 0.000), 636AA (4.0% vs. 0.7%; P = 0.007), 636AG (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (30.9% vs. 20.8%; P = 0.000) and 636A (13.0% vs. 5.8%; P = 0.000) allele in the CIS group are significantly higher than those in the controls. The frequencies of CYP2C19 681AA (16.7% vs. 8.6%; P = 0.036), CYP2C19 636AA (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (36.4% vs. 27.6%; P = 0.023) and CYP2C19 636A (17.5% vs.10.3%; P = 0.010) allele in the recurrent stroke group are significantly higher than those in the first onset group. Multivariate logistic regression analysis of risk factors for cerebral ischemic stroke and recurrent stroke respectively suggests that the CYP2C19 681AA genotype may be an independent risk factor for CIS (OR = 6.179, 95% CI: 2.285 ~ 16.708; P = 0.000) and recurrent stroke (OR = 2.305, 95% CI: 1.121 ~ 4.743; P = 0.023).ConclusionsThe AA genotype and A allele of CYP2C19 G681A may be related to the occurrence and recurrence of cerebral ischemic stroke.

Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1

“…Further support is provided by compelling evidence that CYP activity is associated with enhanced local formation of ROS and lipid peroxidation products, which may alter redox signaling pathways and cause oxidative stress-mediated vascular dysfunctions [37] , [38] , [71] , [96] , [97] , [107] . Importantly, they are also consistent with previous studies reporting the association of CYP genetic polymorphisms with different degrees of susceptibility to various cerebrovascular diseases [44] , [46] . In turn, this may reflect the highly polymorphic nature and significant inter-individual and inter-tissue variability in the expression and activity of CYP enzymes, and the consequent variability in the occurrence of local oxidative stress events [39] , [48] , [108] .…”

“…Indeed, it has been demonstrated that variations in the expression and activity of CYPs can influence the local regulation of cerebral blood flow and vascular homeostasis, and contribute to cerebrovascular diseases [44] , [45] . Consistently, genetic polymorphisms in several CYPs have been associated with inter-individual differences in susceptibility to various vascular and neurological disorders [39] , [46] , [47] , [48] .…”

Cigarette smoking might weaken the prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction patients

“…The CYP2C19*2 polymorphism was detected by PCR–RFLP analysis, and the platelet function was assessed using conventional aggregometry. A great many of previous studies focused on the relationship between CYP2C19 polymorphism and clopidogrel therapy – related diseases also adopted these technologies, and reported comparable results 31, 32. These might support the validity of our detection on the CYP2C19*2 polymorphism and the platelet function.…”

Clustering of ABCB1 and CYP2C19 Genetic Variants Predicts Risk of Major Bleeding and Thrombotic Events in Elderly Patients with Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel

“…In particular, CYP2C19 *2 and *3 (LOF) alleles are associated with a reduced response to standard doses [ 13 , 30 , 31 ]. Notably, a recent study of a Chinese population suggests that CYP2C19 *2 alleles are related to the occurrence and recurrence of cerebral ischaemic stroke [ 32 ]. The major finding of our study is that the combination of three polymorphisms ( CYP2C19 LOF and GOF alleles and ABCB1 C3435T allele) can identify patients at increased risk of developing not only thrombotic events but also major bleeding.…”