GENETIC VARIATION IN THE DDAH-1 GENE IN RELATION TO ADMA LEVELS AND ENDOTHELIAL FUNCTION: PP.6.251

Abstract

Background: Asymmetric dimethylarginine (ADMA), an endogenous methylated amino acid, has been identified as a competitive inhibitor of nitric oxide synthase (NOS). Elevated ADMA levels have been demonstrated in cardiovascular disorders and many studies have reported an inverse correlation between ADMA and endothelial function. The majority of ADMA is metabolized by dimethylarginine dimethylaminohydrolases (DDAH-1 and DDAH-2). Our aim was to study the genetic variation in the DDAH-1 gene in relation to ADMA levels and endothelial function. Methods: A total of 959 individuals, aged 70, from the community based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study were included. Plasma concentrations of ADMA were measured by high performance liquid chromatography. Endothelial function was evaluated with both the invasive forearm technique (measuring endothelial dependent vasodilation in resistance arteries) and with brachial artery ultrasound (measuring flow mediated dilation in a conduit artery). Forty common single nucleotide polymorphisms (SNPs) in the DDAH-1 gene were analyzed. Results: There were significant associations between DDAH-1 genotype and ADMA levels in 20 of the 40 selected SNPs. However, no associations were seen between DDAH-1 genotype and endothelial function. Conclusion: These results indicate that genetic variation in the DDAH-1 gene has an impact on ADMA concentration in plasma. However, it does not seem to have a major influence on endothelial function.