Genetic Variants Predict Outcomes After t-PA Treatment

Two single nucleotide polymorphisms correlate with hemorrhagic transformation, in-hospital death

MONDAY, June 18 (HealthDay News) -- Two genetic variants have been identified that are associated with hemorrhagic transformation (HT) and mortality rates after infusion of tissue plasminogen activator (t-PA) in patients with acute ischemic stroke, according to research published online June 9 in the Annals of Neurology.

Alberto del Rio-Espinola, Ph.D., of the Vall d'Hebrón Hospital in Barcelona, Spain, and colleagues conducted a prospective study using SNPlex to genotype 140 single nucleotide polymorphisms (SNPs) from 97 candidate genes in three patient cohorts. The cohorts included 1,172 patients who were treated with t-PA after acute ischemic stroke. Of these patients, 20.9 percent developed HT and 10.6 percent died. A clinical-genetic model was generated to predict t-PA response.

In replication analysis, the researchers found that the SNP rs669 in alpha-2-macroglobulin (A2M) correlated with HT and withstood Bonferroni correction; and rs1801020 of F12 correlated with in-hospital death. A logistic regression-based predictive model significantly predicted both HT occurrence and in-hospital mortality, and was validated in an independent cohort. The rs669 SNP was associated with modified A2M serum levels at baseline and after t-PA infusion, but did not affect mRNA expression or protein structure. The rs1801020 SNP was associated with altered factor XII activity both before and after t-PA treatment.

"The calculation of HT risk could allow clinicians to individualize fibrinolytic treatment, increasing the therapeutic window for low-risk patients, and more accurately define t-PA risk versus benefit in high-risk individuals," the authors write. "This study might be the first step in the development of personalized medicine and new coadjuvant treatments for t-PA."

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