Association of DIAPH1 gene polymorphisms with ischemic stroke

Area of Science:

• Genetics and Genomics
• Cardiovascular Diseases
• Molecular Biology

Background:

• DIAPH1, a formin protein, is crucial for actin polymerization and plays a role in vascular remodeling and thrombosis.
• Understanding the genetic basis of hypertension and stroke is vital for developing targeted prevention and treatment strategies.

Purpose of the Study:

• To investigate the association between DIAPH1 single-nucleotide polymorphisms (SNPs) and the risk of hypertension and stroke.
• To analyze DIAPH1 mRNA expression levels in ischemic stroke patients.

Main Methods:

• Case-control study involving 2,012 hypertensive patients, 2,210 controls, 2,966 stroke cases (including ischemic and hemorrhagic subtypes), and 2,590 controls.
• Cohort study with 4,098 individuals.
• Comparison of DIAPH1 mRNA expression between 66 ischemic stroke patients (small artery occlusion and large-artery atherosclerosis subtypes) and 58 controls using logistic and Cox regression analysis.

Main Results:

• The rs7703688 T>C variation in DIAPH1 was significantly associated with an increased risk of ischemic stroke (OR: 1.721, P=4.139×10⁻¹²).
• This association was validated in the cohort study, with adjusted hazard ratios of 1.385 (P=0.049) for the additive model and 2.882 (P=0.042) for the recessive model.
• DIAPH1 mRNA expression was significantly downregulated in ischemic stroke patients. A trend towards increased DIAPH1 expression was observed in the small artery occlusion subtype among rs251019 genotypes (P=0.048).

Conclusions:

• DIAPH1 genetic variations contribute to the genetic susceptibility to stroke risk, particularly the small artery occlusion subtype of ischemic stroke.
• Reduced DIAPH1 expression in stroke patients suggests a potential role in the disease's pathogenesis.