This Article Full Text Full Text (PDF) All Versions of this Article: 38/1/6    most recent 01.STR.0000252121.56643.4av1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hoppe, C. Search for Related Content PubMed PubMed Citation Articles by Hoppe, C. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Stroke Related Collections Genetics of Stroke Related Article

(Stroke. 2007;38:6.)
© 2007 American Heart Association, Inc.

Editorials

From Bench to Bedside and Back

The Value of Candidate Gene Association Studies in Translational Research

Carolyn Hoppe, MD

From the Department of Hematology/Oncology, Children’s Hospital & Research Center Oakland, Calif.

Correspondence to Carolyn Hoppe, MD, Department of Hematology/Oncology, Children’s Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA 94609. E-mail choppe@mail.cho.org

See related article, pages 41–49

Key Words: pediatric stroke • risk factors • stroke • stroke in children • stroke in young adults • genetic modifiers

An extract of the first 250 words of the full text is provided, because this article has no abstract.

A major challenge in genetic association studies is the choice of appropriate candidate genes based on plausible biologically driven hypotheses. The current study by Voetsch and coworkers¹ in this issue of Stroke illustrates how the integration of traditional epidemiological approaches, such as case-control studies, and experimental data from the laboratory can be used to assess the role of genetic factors in disease causation. Plasma glutathione peroxidase (GPx-3) is a selenocysteine-containing protein with antioxidant and antithrombotic properties. A familial deficiency in GPx-3 activity has been reported in children with idiopathic stroke, suggesting that polymorphisms in the plasma GPx-3 promoter gene may modify stroke risk.

The authors previously identified a novel, functional transcription start site in the GPx-3 gene with a promoter regulated by hypoxia², prompting further analyses of this candidate gene. In the present study, the authors postulate that by influencing GPx-3 transcription and plasma GPx-3 enzyme levels, distinct variants in the GPx-3 gene may be influencing the pathogenesis of nonatherogenic stroke.

To test the hypothesis that GPx-3 promoter polymorphisms contribute to nonatherosclerotic stroke risk in children and young adults, the effect of GPx-3 polymorphisms on stroke risk was comprehensively assessed in 2 independent study populations. In the initial cohort, comprised of 123 young adult stroke patients and 123 healthy control subjects matched by age, gender and ethnicity, the frequencies of GPx-3 promoter variants were compared, and 2 common haplotypes, H1 and H2, were identified. The H2 haplotype (H2) was present in 13% of the affected and 7% of unaffected . . . [Full Text of this Article]

Related Article:

Promoter Polymorphisms in the Plasma Glutathione Peroxidase (GPx-3) Gene: A Novel Risk Factor for Arterial Ischemic Stroke Among Young Adults and Children

Barbara Voetsch, Richard C. Jin, Charlene Bierl, Kelly S. Benke, Gili Kenet, Paolo Simioni, Filomena Ottaviano, Benito P. Damasceno, Joyce M. Annichino-Bizacchi, Diane E. Handy, and Joseph Loscalzo
Stroke 2007 38: 41-49. [Abstract] [Full Text] [PDF]