Association Between CYP2C19 Genotypes With Clinical Phenotypes and Adipokine Levels Among Ischemic Stroke Patients: A...

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Research
• Metabolic Syndrome

Background:

• The Cytochrome P450 (CYP450) system is involved in vascular diseases, including stroke, by metabolizing drugs and endogenous compounds.
• Adipokines, such as leptin (pro-inflammatory) and adiponectin (anti-inflammatory), are linked to stroke pathogenesis.
• CYP2C19 genetic variants influence the metabolism of various substances, potentially impacting stroke risk and outcomes.

Purpose of the Study:

• To investigate the association between CYP2C19 genetic variants and the occurrence of ischemic stroke.
• To evaluate the relationship between CYP2C19 polymorphisms, adipokine levels (leptin and adiponectin), and stroke outcomes.
• To determine if CYP2C19 genotype influences the composite outcome of stroke recurrence, new ischemic stroke, or death.

Main Methods:

• Prospective recruitment of 204 ischemic stroke patients and 101 controls.
• Genotyping of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *17, *3, *4) using TaqMan assays and DNA sequencing.
• Measurement of serum leptin and adiponectin levels via enzyme-linked immunosorbent assay (ELISA).
• Statistical analysis comparing stroke patients vs. controls and different CYP2C19 metabolizer phenotypes (IM/PM vs. EM/UM).

Main Results:

• SNP2 showed a significant positive association with stroke occurrence.
• Haplotypes AC and GT (SNP1/SNP2) were strongly associated with ischemic stroke occurrence, even after adjusting for age and sex.
• The AC haplotype was significantly associated with the composite outcome (stroke recurrence, new ischemic stroke, or death) and death.
• Stroke patients exhibited significantly higher leptin and lower adiponectin levels compared to controls.
• Leptin levels were higher in intermediate/poor metabolizer (IM/PM) CYP2C19 phenotypes, who also showed a trend towards a higher composite outcome incidence.

Conclusions:

• CYP2C19 polymorphisms may play a significant role in the pathogenesis of ischemic stroke.
• Leptin could be a potential biomarker for atherosclerosis and inflammation in the early post-stroke period.
• Further research with larger sample sizes is warranted to confirm these findings and elucidate the mechanisms involved.