Investigating CYP2C19 loss-of-function allele statuses and their association with stroke of different etiologies in a Taiwanese population.

BACKGROUND: CYP2C19 loss-of-function single-nucleotide polymorphisms (SNPs) are associated with poor responses of clopidogrel in secondary prevention of ischemic stroke (IS). It is still unclear whether these SNPs, which may result in poor cytochrome P450 2C19 (CYP2C19) enzymatic activity, affect the occurrence of IS and its subtypes. The present study evaluated the relationship between the CYP2C19 loss-of-function alleles and IS.

METHODS: Eight-hundred-and-sixty-eight patients with IS and 557 non-stroke (NS) control individuals were prospectively recruited. Stroke etiologies, including large-artery atherosclerosis (LAA), cardioembolism (CE) and small-vessel occlusion (SVO), were determined. The two most common CYP2C19 loss-of-function alleles worldwide, CYP2C19*2 and CYP2C19*3, were investigated by genotyping. Patients with two loss-of-function alleles of the CYP2C19 genes were classified as poor metabolizers.

RESULTS: Our population has a high frequency of CYP2C19 loss-of-function alleles, mostly contributed by CYP2C19*2, being present in 51.3-57.5% of patients with IS of different etiologies and 53.1% of NS individuals. The proportions of CYP2C19 poor metabolizers within NS group and each IS group with disparate etiology are similar [NS 73 (13.1%); LAA 44 (14.2%), p=0.623; CE 26 (14.0%), p=0.541; SVO 38 (13.3%), p = 0.443]. Nevertheless, the frequencies of CYP2C19*3 allele were different among the NS and different IS subgroups. Multivariate analyses adjusting for age, sex and vascular risk factors revealed that CYP2C19*3 allele was a protective factor for SVO [OR=0.5, 95% CI=0.3-0.9, p=0.015 (versus NS), OR=0.5, 95% CI=0.3-0.8, p=0.010 (versus LAA and CE)].

CONCLUSION: The CYP2C19 poor metabolizer is not associated with IS and its subtypes. Furthermore, CYP2C19*3 may be a protective factor for SVO and its mechanism warrants further investigation.This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).