Ischemic Stroke and Six Genetic Variants in CRP, EPHX2, FGA, and NOTCH3 Genes: A Meta-Analysis.
BACKGROUND
Ischemic stroke (IS) is a leading cause of death and disability worldwide. As genetic heritability for IS is estimated at about 35%-40%, the identification of genetic variants associated with IS risk is of great importance. The main objective of this study was to carry out a meta-analysis for polymorphisms in CRP, EPHX2, FGA, and NOTCH3 genes and the risk for IS.


METHODS
Literature search for 6 candidate polymorphisms and IS was conducted using HuGE Navigator, PubMed, and Google Scholar databases. Meta-Analyst program was used to calculate pooled odds ratios (ORs) with a random effects model.


RESULTS
Twenty-five published studies for 6 candidate polymorphisms were included: CRP-rs1800947 (5 studies), CRP-rs1205 (3 studies), EPHX2-rs751141 (5 studies), FGA-rs6050 (6 studies), NOTCH3-rs3815188 (3 studies), and NOTCH3-rs1043994 (3 studies), for a total number of 7,825 IS cases and 56,532 control subjects. We did not find significant pooled ORs (P values > .05) for any of the genetic variants evaluated in this work.


CONCLUSIONS
Our meta-analysis results did not show significant associations between these 6 polymorphisms in 4 candidate genes and IS, despite the functional role of some of these single nucleotide polymorphisms (e.g., rs6050 in FGA gene). Future studies are needed to identify additional main genetic risk factors for IS in different populations.
Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.
Yeimy
Y
González-Giraldo
Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia; Universidad Científica del Sur, Lima, Peru; Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile.
George E
GE
Barreto
Department of Medicine, University of Verona, Verona, Italy; Department of Clinical Sciences, University of Lund, Malmö, Sweden.
Cristiano
C
Fava
Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia; Laboratory of NeuroPsychiatric Genetics, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia. Electronic address: diego.forero@uan.edu.co.
Diego A
DA
Forero
D002545:Brain Ischemia / Q000150:complications / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics*; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D004851:Epoxide Hydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D011454:Prostaglandins A / Q000235:genetics*; D000071656:Receptor, Notch3 / Q000235:genetics*; D020521:Stroke / Q000209:etiology / Q000235:genetics
D011454:Prostaglandins A; D000071656:Receptor, Notch3; D002097:C-Reactive Protein; D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human
Candidate gene; genetic factors; ischemic stroke; meta-analysis; polymorphism; risk factor