The rs2108622 polymorphism is related to the early risk of ischemic stroke in non-valvular atrial fibrillation subjects under oral anticoagulation

Abstract

Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS. Clinical variables, CHADS2-VASC score and data about the international normalized ratio (INR) within the therapeutic range were all recorded. DNA was extracted from blood and genotyping was carried out by DNA sequencing. The main endpoint was the time from VKA onset to IS. Of a total of 356 consecutive IS patients monitored, 33 were included in the study. The median time to the event was 2248.0 days (interquartile range [IQR] 896.3-3545.3). The median CHADS2-VASC score was 4.0 (IQR 3.0-6.0). When we considered the risk of IS within 2 years under VKA treatment, we found that only the rs2108622 AA genotype was significantly associated with this endpoint (early IS) (hazard ratio 6.81, 95% CI 1.37-33.92, p = 0.019). Kaplan-Meier curve analysis also showed a significant relationship between early IS and rs2108622 AA genotype (Log rank p = 0.022). The CYP4F2 gene rs2108622 polymorphism was associated with a risk of early IS in NV-AF patients under VKA treatment.

Genetic Variants of CYP4F2 Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China

“…There are relatively many studies on associations between CYP4F2 -rs2108622 and susceptibility to various cardiovascular diseases including ischemic stroke. 18 , 21 , 22 Considering that the minimum allele frequency of rs2108622 is significantly different in populations with different genetic backgrounds, it is necessary to study the relationship between rs2108622 and IS risk in different populations. There are no related studies have been reported among the Han population from southern China.…”

Genetic variants in CYP4F2 were significantly correlated with susceptibility to ischemic stroke

“…The results showed that the ‘GG’ genotype of CYP4F2 rs2108622 was correlated with an increased risk of IS. In addition, Colàs-Campàs L et al [29] found rs2108622 ‘AA’ genotype in CYP4F2 gene was significantly associated with a risk of early IS in non-valvular atrial fibrillation patients under vitamin K antagonists treatment. However, study based on this CYP4F2 gene is rare.…”