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Association Between Prekallikrein and Stroke: A Mendelian Randomization Study.

Yinan Wang1, Yiming Jia1, Qingyun Xu1

  • 1Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Suzhou Medical College of Soochow University Suzhou China.

Journal of the American Heart Association
|August 15, 2023
PubMed
Summary

High plasma prekallikrein levels, predicted by genetics, are linked to increased risks of all-cause stroke, ischemic stroke, cardioembolic stroke, and small vessel stroke. This suggests prekallikrein plays a key role in stroke development.

Keywords:
Mendelian randomizationischemic strokeprekallikreinstroke

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Area of Science:

  • Genetics
  • Cardiovascular Science
  • Neurology

Background:

  • Previous studies suggest a link between high plasma prekallikrein and stroke risk.
  • The causal relationship remains uncertain.

Purpose of the Study:

  • To investigate the causal associations of genetically predicted plasma prekallikrein concentrations with various stroke types.
  • Utilizing a 2-sample Mendelian randomization approach.

Main Methods:

  • Employed seven independent single-nucleotide polymorphisms as genetic instruments for prekallikrein.
  • Analyzed summary statistics from large-scale genome-wide association studies for stroke and intracerebral hemorrhage (ICH).
  • Applied the inverse-variance weighted method for association estimation.

Main Results:

  • Genetically predicted higher plasma prekallikrein was significantly associated with increased risks of all-cause stroke, ischemic stroke, cardioembolic stroke, and small vessel stroke.
  • No significant associations were found for large artery stroke or ICH.
  • Odds ratios per standard deviation increase in prekallikrein ranged from 1.04 to 1.11 for significant associations.

Conclusions:

  • Genetically predicted high plasma prekallikrein concentrations are causally associated with an elevated risk of several stroke types.
  • Prekallikrein may play a critical role in the pathogenesis of stroke, particularly ischemic subtypes.