title: Polymorphisms in the promoter region of the dimethylarginine dimethylaminohydrolase 2 gene are associated with prevalence of hypertension.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University, Erlangen-Nuremberg, Germany. renke.maas@pharmakologie.uni-erlangen.de
authors: Renke
authors: R
authors: Maas
authors: Jeanette
authors: J
authors: Erdmann
authors: Nicole
authors: N
authors: Lüneburg
authors: Jan
authors: J
authors: Stritzke
authors: Edzard
authors: E
authors: Schwedhelm
authors: Christa
authors: C
authors: Meisinger
authors: Annette
authors: A
authors: Peters
authors: Joachim
authors: J
authors: Weil
authors: Heribert
authors: H
authors: Schunkert
authors: Rainer H
authors: RH
authors: Böger
authors: Wolfgang
authors: W
authors: Lieb
mesh_terms: D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics
chemical_list: D000581:Amidohydrolases; C059999:dimethylargininase