Polymorphisms in the promoter region of the dimethylarginine dimethylaminohydrolase 2 gene are associated with prevalence of hypertension.
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.
Maas
Renke
R
Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University, Erlangen-Nuremberg, Germany. renke.maas@pharmakologie.uni-erlangen.de
Erdmann
Jeanette
J
Lüneburg
Nicole
N
Stritzke
Jan
J
Schwedhelm
Edzard
E
Meisinger
Christa
C
Peters
Annette
A
Weil
Joachim
J
Schunkert
Heribert
H
Böger
Rainer H
RH
Lieb
Wolfgang
W
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
D000581:Amidohydrolases; C059999:dimethylargininase