Polymorphism of CYP2C19 and ABCB1 genes associated with changes in the activity of clopidogrel in patients with ischemic stroke: clinical and ethnic aspects

Aim

To compare the frequency of polymorphisms CYP2C19 and ABCB1 in patients with ischemic stroke and healthy volunteers and to evaluate the effect of concomitant drug therapy on the activity of clopidogrel in patients with ischemic stroke.

Material and methods

One hundred twenty one patients with ischemic stroke and 250 healthy volunteers were genotyped by CYP2C19 and ABCB1 using the real-time polymerase chain reaction. We also studies the changes in the antiplatelet activity of clopidogrel depending on concomitant therapy in patients with ischemic stroke.

Results

In patients with ischemic stroke, the distribution of all studied genotypes was consistent with Hardy-Weinberg law: CYP2C19*2 (χ 2 =0,0001, p=0.99), CYP2C19*3 (χ 2 =0,03, p=0,85), CYP2C19*17 (χ 2 = 0,96, p=0,33), ABCB1 (χ 2 =1,81, p=0,18). In healthy volunteers, the distribution of genotypes was consistent with Hardy-Weinberg law for CYP2C19*2 (Russian: χ 2 =0,025, p=0,87; Buryat: χ 2 =1,90, p=0,17), CYP2C19*17 (Russian: χ 2 =0,28, p=0,60; Buryats: χ 2 =0,86, p=0,35), ABCB1 (Russian: χ 2 =3,58, p=0,06; Buryat: χ 2 =2,51, p=0,11). CYP2C19*3 was not identified in the Russian volunteers. There were statistically significant differences in the frequency of alleles and genotypes of CYP2C19*17 and ABCB1 between patients with stroke and healthy volunteers: the polymorphic markers of CYP2C19*17 (CT + TT) and ABCB1 (CT + TT) were more common in patients with stroke: 43,0% vs. 30,0% (p=0,015), and 82,0% vs. 72,4% (p= 0,054), respectively.

Conclusion

We showed statistically significant differences in the frequency of CYP2C19*3 and CYP2C19*17 between Russians and Buryats of Angara region (healthy volunteers). In patients with ischemic stroke, CYP2C19*17 (CT + TT) and ABCB1 (CT + TT) were more common than in healthy volunteers. A statistically significant decrease in the activity of clopidogrel was found in patients who were treated with thrombolytics within the first hours after admission, calcium channel blockers, ACE inhibitors, and statins.

Key words

Ischemic stroke, CYP2C19 gene, ABCB1 gene, clopidogrel, calcium channel blockers, thrombolytic therapy, proton pump inhibitors, statins, beta-blockers, angiotensin-converting enzyme inhibitors.