Journal Article

Matrix Gla protein polymorphism rs1800801 associates with recurrence of ischemic stroke

Schirmer, Clemens M., Zand, Ramin, Kolinovsky, Amy N., Sofoluke, Nelson, Gupta, Mudit, Rost, Natalia S., Kunaprayoon, Saran, Faber, James E., Kirchner, H. Lester, Griessenauer, Christoph J., Hendrix, Philipp, Person, Thomas N., Goren, Oded, Adams, Matthew

2020

Overview

The MGP single nucleotide polymorphism (SNP) rs1800801 has previously been associated with recurrent ischemic stroke in a Spanish cohort. Here, we tested for association of this SNP with ischemic stroke recurrence in a North American Caucasian cohort. Acute ischemic stroke patients admitted between 10/2009 and 12/2016 at three hospitals within a large healthcare system in the northeastern United States that were enrolled in a healthcare system-wide exome sequencing program were retrospectively reviewed. Patients with recurrent stroke within 1 year after index event were compared to those without recurrence. Of 9,348 suspected acute ischemic strokes admitted between 10/2009 and 12/2016, 1,727 (18.5%) enrolled in the exome-sequencing program. Among those, 1,068 patients had exome sequencing completed and were eligible for inclusion. Recurrent stroke within the first year of stroke was observed in 79 patients (7.4%). In multivariable analysis, stroke prior to the index stroke (OR 9.694, 95% CI 5.793-16.224, p ≤ 0.001), pro-coagulant status (OR = 3.563, 95% CI 1.504-8.443, p = 0.004) 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 the first year. The AA genotype of the MGP SNP rs1800801 is associated with recurrence within the first year after ischemic stroke in North American Caucasians. Study of stroke subtypes and additional populations will be required to determine if incorporation of allelic status at this SNP into current risk scores improves prediction of recurrent ischemic stroke.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Aged, 80 and over / Biology and Life Sciences / Brain Ischemia - genetics / Calcification / Calcium-Binding Proteins - genetics / Cardiovascular disease / Coagulants / Electronic health records / Exome Sequencing / Extracellular Matrix Proteins - genetics / Female / Gene polymorphism / Genetic aspects / Genetic Predisposition to Disease / Genotype / Genotype & phenotype / Health aspects / Health care / Health risk assessment / Humans / Ischemia / Male / Matrix Gla Protein / Medicine / Medicine and Health Sciences / Middle Aged / Neurosurgery / Nucleotides / Patient outcomes / Patients / Physical Sciences / Polymorphism / Polymorphism, Single Nucleotide / Proteins / Recurrence / Recurrence (Disease) / Research and Analysis Methods / Risk Factors / Sequences / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Statistical analysis / Stroke / Stroke - genetics / University faculty