Abstract Body: Introduction: Strokes lead to acute deficits with wide-ranging severity. Genetic variation may explain some of these inter-subject differences. The current report examined the relationship that candidate genetic variants have with acute injury and acute behavioral deficits. We hypothesized that variants known to be associated with poorer stroke recovery would also be associated with more a severe acute presentation.
Methods: Infarcts were outlined on clinical scans acquired during acute stroke admission as part of the STRONG (“Stroke, sTress, RehabilitatiON, and Genetics”) study and resampled to MNI152 brain standard space. Multivariable linear regression modeling was used to examine association with genetic measures known to be related to stroke outcome: 3 single nucleotide polymorphisms (SNPs): BDNF (rs6265), ACE (rs4291), and FAAH (rs324420), plus ApoE e4 and ApoE e2; a dopamine polygene score was also explored. Acute injury (infarct volume) and acute deficits (NIHSS score, grip strength, and acute stress disorder inventory (ASDI)) were each examined as the dependent measure in separate models that used age, gender, and ancestry as covariates. To understand where in the brain these relationships occurred, voxel lesion symptom mapping (VLSM) was used to test for associations between acute injury and each genetic measure.
Results: In 448 subjects (age 63.4±14.4 yr (mean±SD), 43.1% females), lesion volume ranged from 0.46 to 535.13 cc and involved cortical grey matter in 63% of patients. Larger lesion volume was associated with presence of the ACE SNP (β=8.77, p=0.03); lower NIHSS score, with ApoE e4 (β=-1.69, p=0.04); greater grip strength, with ApoE e2 SNPs (β=6.78, p=0.03); and higher ASDI, with the ACE SNP (β=0.56, p=0.05). VLSM revealed that acute injury to the postcentral gyrus was significantly more likely in the presence of the ACE SNP (z=-3.5), and that acute injury to the calcarine fissure was significantly more likely in the presence of the BDNF SNP (z=-2.53).
Conclusions: Genetic variants known to be associated with differences in stroke recovery are also related to acute stroke deficits and injury. In particular, a common variant in the gene for ACE was associated with differences in lesion volume and location, findings that may suggest a personalized medicine approach to acute therapy. Measures of genetic variability may be useful to understand inter-subject differences in acute injury and symptom severity, and may have therapeutic implications.