Abstract
Introduction:Patients with CKD have elevated plasma levels of Asymmetrical Dimethyl Arginine (ADMA), impaired EDRF/NO responses in isolated resistance vessels, and a marked increase in the frequency of cardiovascular events that are predicated by plasma levels of ADMA. ADMA is considered as a risk factor for endothelial dysfunction, progression of chronic kidney disease and a marked increase in the frequency of cardiovascular events that are predicated by plasma levels of ADMA. Elevated ADMA in CKD have been related to a combination of a reduced renal ADMA excretion and a reduced catabolism of ADMA by dimethylarginine dimethylaminohydrolase (DDAH). The current study was undertaken to determine whether there is a correlation between ADMA and SNPs at -449 DDAH 2.Subjects and Methods :It was a cross sectional analytic study, 56 hemodialysis patients and 30 healthy individuals were enrolled. Based on its etiology, HD patients group was further divided in to hypertension (HT) subgroup and non-HT subgroup. Genotyping of the polymorphisms was performed using PCR-based SNP detection methods based on 5’-exonuclease activity assays for rs805305.Results :Heterozygotes were observed as the most abundant genotypes in both groups, followed by GG genotype in the HD patients (30%) and CC (27%) healthy individuals. Among the HT subgroup, the mean plasma levels of ADMA were sequentially higher from genotypes CC, G/C and GG (p = 0.037). Further multiple comparisons between groups using post hoc test showed results that genotype GG and CC were different at 0.05 level of significance. These findings were not found among non HT subgroup.Conclusion: Genetic variation in the DDAH 2 genes is significantly associated with serum ADMA levels in hypertensive HD patients. We observed that carriage of a G at position -449 in the promoter region of the DDAH 2 gene is associated with higher ADMA levels.
Highlights
Patients with chronic kidney disease (CKD) have elevated plasma levels of Asymmetrical Dimethyl Arginine (ADMA), impaired EDRF/nitric oxide (NO) responses in isolated resistance vessels, and a marked increase in the frequency of cardiovascular events that are predicated by plasma levels of ADMA
ADMA is considered as a risk factor for endothelial dysfunction, progression of chronic kidney disease and a marked increase in the frequency of cardiovascular events that are predicated by plasma levels of ADMA
Genetic variation in the dimethylarginine dimethylaminohydrolase (DDAH) 2 genes is significantly associated with serum ADMA levels in hypertensive HD patients
Summary
Patients with CKD have elevated plasma levels of Asymmetrical Dimethyl Arginine (ADMA), impaired EDRF/NO responses in isolated resistance vessels, and a marked increase in the frequency of cardiovascular events that are predicated by plasma levels of ADMA. ADMA is considered as a risk factor for endothelial dysfunction, progression of chronic kidney disease and a marked increase in the frequency of cardiovascular events that are predicated by plasma levels of ADMA. Further multiple comparisons between groups using post hoc test showed results that genotype GG and CC were different at 0.05 level of significance. These findings were not found among non HT subgroup. The mechanisms of endothelial vasodilator dysfunction (EVD) are likely multi-factorial [5] Evidences from both animal models and clinical studies suggests that accumulation of the endogenous nitric-oxide synthase (NOS) inhibitors, ADMA and NGmethyl-L-arginine (LNMMA) contributes to reducing nitric oxide (NO) [6,7].
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