Population-specific associations of deleterious rare variants in coding region of P2RY1–P2RY12 purinergic receptor genes in large-vessel ischemic stroke patients

Piotr K. Janicki, Ceren Eyileten, Victor Ruiz-Velasco, Khaled Anwar Sedeek, Justyna Pordzik, Anna Czlonkowska, Iwona Kurkowska-Jastrzebska, Shigekazu Sugino, Yuka Imamura-Kawasawa, Dagmara Mirowska-Guzel, Marek Postula

研究成果: Article

5 引用 (Scopus)

抜粋

The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. The genes selected for re-sequencing consisted of 26 genes coding for proteins associated with the surface membrane of platelets. Targeted pooled re-sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of large-vessel IS) and 500 controls. After quality control and prioritization based on allele frequency and damaging probability, follow-up individual genotyping of deleterious rare variants was performed in patients from the original cohort. Gene-based analyses identified an association between IS and 6 rare functional and damaging variants in the purinergic genes (P2RY1 and P2RY12 locus). The predicted properties of the most damaging rare variants in P2RY1 and P2RY12 were confirmed by using mouse fibroblast cell cultures transfected with plasmid constructs containing cDNA of mutated variants (FLIPR on FlexStation3). This study identified a putative role for rare variants in P2RY1 and P2RY12 genes involved in platelet reactivity on large-vessel IS susceptibility in a Polish population.

元の言語English
記事番号2678
ジャーナルInternational journal of molecular sciences
18
発行部数12
DOI
出版物ステータスPublished - 2017 12 11
外部発表Yes

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

フィンガープリント Population-specific associations of deleterious rare variants in coding region of P2RY1–P2RY12 purinergic receptor genes in large-vessel ischemic stroke patients' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Janicki, P. K., Eyileten, C., Ruiz-Velasco, V., Sedeek, K. A., Pordzik, J., Czlonkowska, A., Kurkowska-Jastrzebska, I., Sugino, S., Imamura-Kawasawa, Y., Mirowska-Guzel, D., & Postula, M. (2017). Population-specific associations of deleterious rare variants in coding region of P2RY1–P2RY12 purinergic receptor genes in large-vessel ischemic stroke patients. International journal of molecular sciences, 18(12), [2678]. https://doi.org/10.3390/ijms18122678