The Functional Polymorphism of DDAH2 rs9267551 Is an Independent Determinant of Arterial Stiffness

Frontiers in Cardiovascular Medicine

Giorgio Sesti¹  Rosangela Spiga²  Teresa Vanessa Fiorentino²  Sofia Miceli²  Elettra Mancuso²  Maria Perticone²  Carolina Averta²  Gaia Chiara Mannino²  Francesco Andreozzi³  Elena Succurro³  Angela Sciacqua³  Prapaporn Jungtrakoon Thamtarana⁴ 

[1] Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy;Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy;Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy;Siriraj Center of Research Excellence for Diabetes and Obesity, Division of Molecular Medicine, Department of Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;

关键词: pulse wave velocity;    arterial stiffness;    dimethylarginine dimethylaminohydrolase;    rs9267551;    ADMA;   

DOI  :  10.3389/fcvm.2021.811431

来源: DOAJ

【 摘 要 】

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA.Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels.Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.

【 授权许可】

Unknown