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Genetic variation in the dimethylarginine dimethylaminohydrolase 1 gene (DDAH1) is related to asymmetric dimethylarginine (ADMA) levels, but not to endothelium-dependent vasodilation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .ORCID iD: 0000-0003-2256-6972
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
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2013 (English)In: Vascular Medicine, ISSN 1358-863X, E-ISSN 1477-0377, Vol. 18, no 4, 192-199 p.Article in journal (Refereed) Published
Abstract [en]

Objectives:

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. The breakdown of ADMA is mainly governed by the activity of dimethylarginine dimethylaminohydrolases (DDAHs). We investigated if genetic variation in the DDAH1 and DDAH2 genes were related to ADMA and l-arginine levels, as well as measures of endothelium-dependent vasodilation.

Methods:

In 1016 70-year-old participants of the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (50% women), we measured endothelium-dependent vasodilation (EDV) using the invasive forearm technique with acetylcholine given in the brachial artery and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). Plasma l-arginine and ADMA levels were measured by high-performance liquid chromatography and 55 single nucleotide polymorphisms (SNPs) in the DDAH1 and DDAH2 genes were genotyped.

Results:

Several of the genotypes in the DDAH1 gene were highly significantly related to ADMA levels (p = 10−7 at best), but not to the l-arginine levels. No relationships between the genotypes in the DDAH2 gene and ADMA or l-arginine levels were found. None of the DDAH1 genotypes being closely related to ADMA levels were significantly related to EDV or FMD. Neither were any of the DDAH2 genotypes closely related to any of the measurements of vasoreactivity.

Conclusion:

A close relationship was seen between SNPs in the DDAH1, but not DDAH2, gene and ADMA levels. However, variation in those genes was not related to measures of EDV in this elderly population.

Place, publisher, year, edition, pages
2013. Vol. 18, no 4, 192-199 p.
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-207894DOI: 10.1177/1358863X13496488ISI: 000323328500003PubMedID: 23892448OAI: oai:DiVA.org:uu-207894DiVA: diva2:650225
Available from: 2013-09-20 Created: 2013-09-20 Last updated: 2017-12-06Bibliographically approved

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Lind, LarsIngelsson, ErikKumar, JitenderSyvänen, Ann-ChristineAxelsson, Tomas

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