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Causal Effect of Lipoprotein-Associated Phospholipase A2 Activity on Ischemic Stroke: A Mendelian Randomization Study.
Zhang, Yang; Jiang, Miaowen; Gao, Yuan; Xu, Yi; Zhou, Yifan; Wu, Di; Zhou, Chen; Liu, Guiyou; Li, Ming; Ji, Xunming.
Affiliation
  • Zhang Y; Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China, zy1192268729@163.com.
  • Jiang M; China-America Institute of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China, zy1192268729@163.com.
  • Gao Y; Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
  • Xu Y; School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, China.
  • Zhou Y; Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • Wu D; Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
  • Zhou C; China-America Institute of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • Liu G; Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
  • Li M; Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
  • Ji X; China-America Institute of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Cerebrovasc Dis ; 53(5): 579-587, 2024.
Article in En | MEDLINE | ID: mdl-38113871
ABSTRACT

BACKGROUND:

The relationship between ischemic stroke (IS) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is still unclear, and there is a dearth of stratified research on the relationship between Lp-PLA2 activity and different IS subtypes. Therefore, Mendelian randomization (MR) was used in this study to examine the relationship between genetically proxied Lp-PLA2 activity and the risks of IS and its subtypes.

METHODS:

Based on information from a meta-analysis of genome-wide association studies, which included 13,664 European people, five single nucleotide polymorphisms related to Lp-PLA2 activity were chosen as instrumental variables. Summary statistics information about the MEGESTROKE consortium with the European group (40,585 cases and 406,111 controls) include any IS (AIS; n = 34,217), large-artery stroke (LAS; n = 4,373), cardioembolic stroke (CES; n = 7,193), and small-vessel stroke (SVS; n = 5,386). In order to determine the causal relationships between Lp-PLA2 activity and IS as well as its subtypes, the inverse-variance-weighted (IVW) approach was chosen as the primary analysis. Significant estimates were then tested by sensitivity analysis to rule out heterogeneity and pleiotropy.

RESULTS:

IVW showed that Lp-PLA2 activity was causally associated with LAS (odds ratio = 3.25, 95% confidence interval = 1.65-6.41, p = 0.0007) but not with other subtypes of stroke. Sensitivity analysis for causal estimates between Lp-PLA2 activity and LAS showed no significant heterogeneity or pleiotropy.

CONCLUSIONS:

These MR analyses support a causal effect of Lp-PLA2 activity on LAS but not on AIS, CES, or SVS, which suggests that serum Lp-PLA2 activity might be a biomarker for prediction of LAS.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Predisposition to Disease / 1-Alkyl-2-acetylglycerophosphocholine Esterase / Ischemic Stroke Limits: Humans Language: En Journal: Cerebrovasc Dis Journal subject: ANGIOLOGIA / CEREBRO Year: 2024 Document type: Article Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Predisposition to Disease / 1-Alkyl-2-acetylglycerophosphocholine Esterase / Ischemic Stroke Limits: Humans Language: En Journal: Cerebrovasc Dis Journal subject: ANGIOLOGIA / CEREBRO Year: 2024 Document type: Article Country of publication: Switzerland