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Maas, R.* ; Erdmann, J.* ; Luneburg, N.* ; Stritzke, J.* ; Schwedhelm, E.* ; Meisinger, C. ; Peters, A. ; Weil, J.* ; Schunkert, H.* ; Boger, R.H.* ; Lieb, W.*

Polymorphisms in the promoter region of the dimethylarginine dimethylaminohydrolase 2 gene are associated with prevalence of hypertension.

Pharmacol. Res. 60, (Sp. Iss. SI), 488-493 (2009)
DOI PMC
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Infusion of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) causes an elevation of blood pressure and depression of cardiac output. Polymorphisms in the promoter region of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase 2 (DDAH2) gene have been associated with elevated ADMA concentrations and adverse outcomes in critically ill patients. We hypothesized that two DDAH2 promoter - 1151 A/C and -449 G/C polymorphisms (rs805304 and rs805305) will be associated with blood pressure levels, hypertension prevalence and measures of cardiac structure and function in the general population. Methods and results: We genotyped rs805304 and rs805305 in 783 participants of the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg S3 study. Plasma ADMA concentrations did not differ by rs805304 and rs805305 genotypes. Both polymorphisms were associated with a higher prevalence of hypertension. The odds ratio (adjusted for age, gender and body mass index) for hypertension was 1.70 (95%CI: 1.22-2.36: p=0.002) for those homozygous (n=348) for the -1151A allele and 1.80 (95%CI: 1.29-2.49, p<0.001) for individuals homozygous for the -449G allele (n=350). However, both polymorphisms were not related to measures of cardiac structure and function (left ventricular [LV] mass, LV wall thickness, LV end-diastolic diameter, ejection fraction, E/A ratio, isovolumetric relaxation time) in multivariable-adjusted models. Conclusion: The present study indicates that the -1151 A/C and -449 G/C polymorphisms in the DDAH2 promoter region are not related to plasma ADMA levels or measures of cardiac structure and function but are associated with an increased prevalence of hypertension. The mechanisms of this association need further investigation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter dimethylarginine dimethylaminohydrolase; snp; hypertension; asymmetric dimethylarginine; left-ventricular hypertrophy; nitric-oxide synthesis; asymmetric dimethylarginine; endothelial-cells; heart-disease; men; mortality; plasma; risk; mass
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 1043-6618
e-ISSN 1096-1186
Zeitschrift Pharmacological Research
Quellenangaben Band: 60, Heft: 6, Seiten: 488-493, Artikelnummer: , Supplement: (Sp. Iss. SI)
Verlag Elsevier
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e) G-503900-004
G-504090-001
PubMed ID 19666123
DOI 10.1016/j.phrs.2009.07.013
Scopus ID 70350052828
Erfassungsdatum 2009-12-31
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