| Objective To investigate the correlation between the distribution of cytochrome P450(CYP)2C19gene polymorphism locus G681A and G636A polymorphisms and cerebral ischemic stroke in Chinese Han population from Tian-jin area.Methods The peripheral blood DNA was extracted from299patients with cerebral ischemic stroke and295healthy controls. The genotypic assays of CYP2C19G681A and CYP2C19G636A were conducted using the polymerase chain reaction-restriction fragment length polymorphism. The sampled sequencing was used to verify the correctness of genotyping results. The genotypes and alleles distribution of CYP2C19G681A and CYP2C19G636A were compared using Chi Square in patients with cerebral ischemic stroke and healthy controls. The correlation between CYP2C19G681A and CYP2C19G636A genetic polymorphisms and cerebral ischemic stroke were further analyzed using multivariate logistic regression analysis.Results l.The constituent ratios of hypertension (75.3%vs.25.4%; χ2=147.483, P=0.000), diabetes mellitus (34.4%vs.7.1%; χ2=67.147, P=0.000), ischemic heart disease (35.5%vs.12.2%; x2=44.119, P=0.000), hyperlipidemia (53.8%vs.41.4%; χ2=9.287, P=0.002), smoking (39.8%vs.10.5%; χ2=67.495, P=0.000) and drinking (24.1%vs.6.8%; χ2=33.956, P=0.000), as well as fasting blood-glucose[(7.504±3.461)mmol/L vs.(5.538±0.980) mmol/L; t=9.391, P=0.000], systolic pressure[(153.01±22.593) mmHg vs.(127.82±18.146) mmHg; t=14.971, P=0.000] and diastolic pressure[(86.21±12.644) mmHg vs.(76.51±9.684) mmHg; t=10.489, P=0.000] in the cerebral ischemic stroke group were significantly higher than those in the healthy control group. The level of high-density lipoprotein cholesterol [(1.113±0.562) mmol/L vs.(1.316±0.452) mmol/L; t=-4.842,P=0.000] was significantly lower than it in the healthy control group. There were no significant differences in age, gender, total cholesterol, triglyceride and low-density lipoprotein cholesterol between the cerebral ischemic stroke group and the healthy control group. There were no significant differences in age, gender, smoking, drinking, hypertension, diabetes mellitus, diabetes mellitus, ischemic heart disease, myocardial infarction, blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and fasting blood-glucose between the recurrent stroke group and the first onset group.2. Population genetic survey showed that the distribution of CYP2C19G681A gene polymorphism in the cerebral ischemic stroke group (χ2=1.380, P=0.502), the first onset group (χ2=0.265, P=0.876), the recurrent stroke group (χ2=1.290, P=0.525) and the healthy control group (χ2=1.749, P=0.417) complied with Hardy-Weinberg equilibrium. The distribution of CYP2C19G636A gene polymorphism in the cerebral ischemic stroke group (χ=4.180, P=0.124), the first onset group (χ2=0.930, P=0.628), the recurrent stroke group (x2=3.794, P=0.150) and the healthy control group (χ2=0.400, P=0.819) complied with Hardy-Weinberg equilibrium.3. The frequency of CYP2C19681A allele was25.9%in the overall study population. There were significant differences in the frequency of CYP2C19G681A genotype distribution between the cerebral ischemic stroke group and the healthy control group (χ2=20.137, P=0.000). The genotypes of the two groups are mainly GG. The frequencies of genotype AA (11.7%vs.2.7%; P=0.000) and allele A (30.9%vs.20.8%;P=0.000) in the cerebral ischemic stroke group were significantly higher than those in the healthy control group. The frequencies of genotype AA (16.7%vs.8.6%; P=0.036) and allele A (36.4%vs.27.6%;P=0.023) in the recurrent stroke group were significantly higher than those in the first onset group. The AA genotype and A allele of CYP2C19G681A may be associated with the attack and recurrence of cerebral ischemic stroke.4. The frequency of CYP2C19636A allele was9.4%in the overall study population. There were significant differences in the frequency of CYP2C19G636A genotype distribution between the cerebral ischemic stroke group and the healthy control group (χ2=17.232, P=0.000). The genotypes of the two groups are mainly GG. The frequencies of genotype AA (4.0%vs.0.7%; P=0.007), AG (7.0%vs.2.2%; P=0.038) and allele A (13.0%vs.5.8%;P=0.000) in the cerebral ischemic stroke group were significantly higher than those in the healthy control group. The frequencies of genotype AA(7.0%vs.2.2%; P=0.038) and allele A (17.5%vs.10.3%; P=0.010) in the recurrent stroke group were significantly higher than those in the first onset group. The AA genotype and A allele of CYP2C19G636A may be associated with the attack and recurrence of cerebral ischemic stroke. The AG genotype of CYP2C19G636A may be associated with the attack of cerebral ischemic stroke, but it was not associated with the recurrence of cerebral ischemic stroke.5. There were significant differences in the frequency of CYP2C19G681A0^=7.178, P=0.028) and CYP2C19G636A (χ2=8.720, P=0.013) genotype distributions between males and females in the cerebral ischemic stroke group. The frequencies of CYP2C19681AA genotype (15.8%vs.5.7%; P=0.008), CYP2C19636AA genotype (6.8%vs.0.0%; P=0.003) and A allele of CYP2C19G681A (34.5%vs.25.8%; P=0.025) in males were significantly higher than those in females.6. There were no significant differences in the frequency of CYP2C19G681A genotype (χ2=2.026, P=0.363) and A allele of CYP2C19G681A (χ=1.870, P=0.172) between older than60and younger than60in the cerebral ischemic stroke group. Besides, there were no significant differences in the frequency of CYP2C19G636A genotype (χ2=4.524, P=0.104) and Aallele of CYP2C19G636A (χ2=0.730, P=0.393) between older than60and younger than60in the cerebral ischemic stroke group.7. There were no significant differences in the frequency of CYP2C19G681A genotype (χ2=4.967, P=0.291) and Aallele of CYP2C19G681A(χ2=0.616, P=0.735) between different NIHSS groups in the cerebral ischemic stroke group. Besides, there were no significant differences in the frequency of CYP2C19G636A genotype (χ2=3.239, P=0.519) and A allele of CYP2C19G636A (χ2=1.242, P=0.537) between different NIHSS groups in the cerebral ischemic stroke group.8. There were significant differences in the frequency of CYP2C19G681A genotype (χ2=15.170, P=0.019) between TOAST classification of the cerebral ischemic stroke group. The frequency of genotype AG (60.0%vs.43.9%vs.27.8%vs.26.7%; P=0.010) in the stroke of other determined cause group were significantly higher than those in the large-artery atherosclerosis group, the cardioembolism group and the small-artery occlusion group. But there were no significant differences in the frequency of CYP2C19681AA genotype (χ2=6.915, P=0.075) and A allele of CYP2C19G681A (χ2=2.067, P=0.559) between TOAST classification of the cerebral ischemic stroke group. There were also no significant differences in the frequency of CYP2C19G636A genotype (χ=5.289, P=0.507) and A allele of CYP2C19G636A (χ2=2.697, P=0.441) between TOAST classification of the cerebral ischemic stroke group.9. Multivariate logistic regression analysis of risk factors for cerebral ischemic stroke showed that the CYP2C19681AA genotype was an independent risk factor for cerebral ischemic stroke (odds ratio6.179,95%confidence interval2.285-16.708; P=0.000).10. Multivariate logistic regression analysis of risk factors for recurrent stroke showed that the CYP2C19681AA genotype was an independent risk factor for recurrent stroke (odds ratio2.305,95%confidence interval1.121-4.743; P=0.023), but CYP2C19636AA genotype was not associated with the recurrence of cerebral ischemic stroke (P=0.098).Conclusions1. The AA genotype and A allele of CYP2C19G681A may be an independent risk factor for the occurrence and recurrence of cerebral ischemic stroke in Chinese Han population from Tian-jin area.2. The AA genotype and A allele of CYP2C19G636A may be associated with the attack and recurrence of cerebral ischemic stroke. The AG genotype of CYP2C19G636A may be associated with the attack of cerebral ischemic stroke, but it was not associated with the recurrence of cerebral ischemic stroke.3. The frequencies of CYP2C19681AA and CYP2C19636AA genotype in males were significantly higher than those in females. |
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