Role of platelet gene polymorphisms in ischemic pediatric stroke subtypes: a case-control study

Area of Science:

• Genetics and Molecular Biology
• Pediatric Neurology
• Hematology

Background:

• Pediatric ischemic stroke (IPS) encompasses diverse subtypes, including cerebral sinovenous thrombosis (CSVT), perinatal arterial ischemic stroke (PAIS), and childhood arterial ischemic stroke (CAIS).
• The genetic underpinnings of IPS subtypes are not fully elucidated, necessitating investigation into potential genetic risk factors.

Purpose of the Study:

• To investigate the association of human platelet antigen (HPA) and P-selectin gene (SELP) polymorphisms and haplotypes with factor V (FV) R506Q in pediatric ischemic stroke (IPS) subtypes.
• To determine the specific roles of HPA and SELP genetic variations in the pathogenesis of CSVT, PAIS, and CAIS.

Main Methods:

• A case-control study involving 150 children with IPS and 150 age- and sex-matched controls.
• Genotyping of FV R506Q, HPA-1, HPA-2, HPA-3, and SELP polymorphisms (S290N, V599L, T715P, N562D) using various molecular techniques including CVD StripAssay®, real-time PCR, high-resolution melting analysis, and sequence-specific PCR.

Main Results:

• HPA-1b allele and specific HPA haplotypes (HPA-1a2a3b, HPA-1b2a3a, HPA-1b2b3a) were significantly associated with an increased risk of CSVT.
• The HPA-3b allele demonstrated a protective effect against PAIS and CAIS, while the HPA-1a2b3a haplotype was linked to an increased risk of CAIS.
• A potential synergistic effect between SELP haplotypes and FV R506Q was observed, primarily associated with PAIS, though not reaching statistical significance.

Conclusions:

• Individual human platelet antigens (HPAs), and particularly HPA haplotypes, play a role in the pathogenesis of pediatric ischemic stroke subtypes.
• The study suggests a potential risk-enhancing interaction between SELP haplotypes and factor V R506Q, specifically in perinatal arterial ischemic stroke.