Authors: Saran Kunaprayoon; Philipp Hendrix; Nelson Sofoluke; Matthew Adams; Ramin Zand; Amy Kolinovsky; Thomas Person; Oded Goren; Clemens Schirmer; Natalia Rost; James Faber; Christoph Griessenauer (Scranton, PA)

Introduction: Recurrent ischemic stroke is associated with increased morbidity and mortality. The matrix gamma-carboxyglutamatic acid Gla protein (MGP) is an extracellular matrix protein involved in the inhibition of vascular calcification. The MGP rs1800801 single nucleotide polymorphism (SNP) specifically is associated with recurrent ischemic stroke. Here, we explored the relationship between this SNP and recurrence of ischemic stroke within one year in a Northeastern Pennsylvania cohort. 

Methods: We retrospectively reviewed a cohort of Caucasian acute ischemic stroke patients admitted between 10/2009 and 12/2016 who enrolled in a system-wide exome sequencing program at a large healthcare system in Northeastern Pennsylvania. Patients admitted in 2016 were assessed for recurrent strokes until 12/2017. We then compared the rs1800801 SNP in patients with recurrent stroke within one year against those without recurrent stroke. 

Results: 1,068 patients had ischemic stroke and exome sequencing completed, deeming them eligible for inclusion. 79 (7.4%) patients had recurrent ischemic events.  Multivariable analysis suggested hypercoagulability (OR = 3.563, 95% CI 1.504 – 8.443, p = 0.004), prior stroke (OR 9.694, 95% CI 5.793 – 16.224, p ≤ 0.001), and the AA genotype of SNP rs1800801 (OR = 2.408, 95% CI 1.079 – 4.389, p = 0.004) were independently associated with recurrent stroke within one year.  Family history of stroke shows a positive trend towards recurrent stroke (OR = 1.698, 95% CI 0.988 – 2.916, p = 0.055). 

Conclusion: The AA genotype of the rs1800801 SNP is independently associated with recurrent ischemic stroke within one year among Northeastern Pennsylvania Caucasians. Although risk of recurrence is still undetermined in subgroups of Caucasians, these findings may contribute to the development of preventative measures for patients with high risk genetic profile for recurrent ischemic stroke.