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Mosaic Loss of Chromosome Y Is Associated With Functional Outcome After Ischemic Stroke

Dorvall, Malin ; Pedersen, Annie ; Dumanski, Jan P. ; Söderholm, Martin LU ; Lindgren, Arne G. LU ; Stanne, Tara M. and Jern, Christina (2023) In Stroke 54(9). p.2434-2437
Abstract

BACKGROUND: Mosaic loss of chromosome Y (LOY) is associated with cardiovascular and neurodegenerative diseases in men, and genetic predisposition to LOY is associated with poor poststroke outcome. We, therefore, tested the hypothesis that LOY itself is associated with functional outcome after ischemic stroke. METHODS: The study comprised male patients with ischemic stroke from the cohort studies SAHLSIS2 (Sahlgrenska Academy Study on Ischemic Stroke Phase 2; n=588) and LSR (Lund Stroke Register; n=735). We used binary logistic regression to analyze associations between LOY, determined by DNA microarray intensity data, and poor 3-month functional outcome (modified Rankin Scale score, >2) in each cohort separately and combined.... (More)

BACKGROUND: Mosaic loss of chromosome Y (LOY) is associated with cardiovascular and neurodegenerative diseases in men, and genetic predisposition to LOY is associated with poor poststroke outcome. We, therefore, tested the hypothesis that LOY itself is associated with functional outcome after ischemic stroke. METHODS: The study comprised male patients with ischemic stroke from the cohort studies SAHLSIS2 (Sahlgrenska Academy Study on Ischemic Stroke Phase 2; n=588) and LSR (Lund Stroke Register; n=735). We used binary logistic regression to analyze associations between LOY, determined by DNA microarray intensity data, and poor 3-month functional outcome (modified Rankin Scale score, >2) in each cohort separately and combined. Patients who received recanalization therapy were excluded from sensitivity analyses. RESULTS: LOY was associated with about 2.5-fold increased risk of poor outcome in univariable analyses (P<0.001). This association withstood separate adjustment for stroke severity and diabetes in both cohorts but not age. In sensitivity analyses restricted to the nonrecanalization group (n=987 in the combined cohort), the association was significant also after separate adjustment for age (odds ratio, 1.6 [95% CI, 1.1-2.4]) and when additionally adjusting for stroke severity and diabetes (odds ratio, 1.6 [95% CI, 1.1-2.5]). CONCLUSIONS: We observed an association between LOY and poor outcome after ischemic stroke in patients not receiving recanalization therapy. Future studies on LOY and other somatic genetic alterations in larger stroke cohorts are warranted.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
brain infarction, brain ischemia, chromosomes, genetics, humans, male, stroke
in
Stroke
volume
54
issue
9
pages
4 pages
publisher
American Heart Association
external identifiers
  • pmid:37465995
  • scopus:85169179471
ISSN
0039-2499
DOI
10.1161/STROKEAHA.123.043551
language
English
LU publication?
yes
id
8e497157-f591-4c79-8525-a815128305e4
date added to LUP
2023-10-30 13:59:45
date last changed
2024-04-19 03:03:14
@article{8e497157-f591-4c79-8525-a815128305e4,
  abstract     = {{<p>BACKGROUND: Mosaic loss of chromosome Y (LOY) is associated with cardiovascular and neurodegenerative diseases in men, and genetic predisposition to LOY is associated with poor poststroke outcome. We, therefore, tested the hypothesis that LOY itself is associated with functional outcome after ischemic stroke. METHODS: The study comprised male patients with ischemic stroke from the cohort studies SAHLSIS2 (Sahlgrenska Academy Study on Ischemic Stroke Phase 2; n=588) and LSR (Lund Stroke Register; n=735). We used binary logistic regression to analyze associations between LOY, determined by DNA microarray intensity data, and poor 3-month functional outcome (modified Rankin Scale score, &gt;2) in each cohort separately and combined. Patients who received recanalization therapy were excluded from sensitivity analyses. RESULTS: LOY was associated with about 2.5-fold increased risk of poor outcome in univariable analyses (P&lt;0.001). This association withstood separate adjustment for stroke severity and diabetes in both cohorts but not age. In sensitivity analyses restricted to the nonrecanalization group (n=987 in the combined cohort), the association was significant also after separate adjustment for age (odds ratio, 1.6 [95% CI, 1.1-2.4]) and when additionally adjusting for stroke severity and diabetes (odds ratio, 1.6 [95% CI, 1.1-2.5]). CONCLUSIONS: We observed an association between LOY and poor outcome after ischemic stroke in patients not receiving recanalization therapy. Future studies on LOY and other somatic genetic alterations in larger stroke cohorts are warranted.</p>}},
  author       = {{Dorvall, Malin and Pedersen, Annie and Dumanski, Jan P. and Söderholm, Martin and Lindgren, Arne G. and Stanne, Tara M. and Jern, Christina}},
  issn         = {{0039-2499}},
  keywords     = {{brain infarction; brain ischemia; chromosomes; genetics; humans; male; stroke}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{2434--2437}},
  publisher    = {{American Heart Association}},
  series       = {{Stroke}},
  title        = {{Mosaic Loss of Chromosome Y Is Associated With Functional Outcome After Ischemic Stroke}},
  url          = {{http://dx.doi.org/10.1161/STROKEAHA.123.043551}},
  doi          = {{10.1161/STROKEAHA.123.043551}},
  volume       = {{54}},
  year         = {{2023}},
}