AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA levels and with incidence of coronary artery disease in Egyptians
Date
2018
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Springer Netherlands
Series Info
Molecular Biology Reports
45
45
Scientific Journal Rankings
Abstract
Dimethylarginine aminodehydrolase (DDAH1) and alanine glyoxylate aminotransferase2 (AGXT2) are two enzymes that contribute in asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) metabolism. Hence they affect production and bioavailability of eNOS-derived nitric oxide (NO) and consequently healthy blood vessels. The major aims of the current study were to investigate the association of genetic variants of AGXT2 rs37369, AGXT2 rs16899974 and DDAH1 rs997251 SNPs with incidence of coronary artery disease (CAD) in Egyptians and to correlate these variants with the serum levels of ADMA and SDMA. The study included 150 subjects; 100 CAD patients and 50 healthy controls. Genotyping was performed by qPCR while the ADMA and SDMA concentrations were assayed by ELISA. Both serum ADMA and SDMA concentrations were significantly higher in CAD patients compared to controls (both p < 0.0001). Genotype distributions for all studied SNPs were significantly different between CAD patients and controls. Carriers of AGXT2 rs37369-T allele (CT + TT genotypes) and AGXT2 rs16899974-A allele (CA + AA genotypes) had 2.4- and 2.08-fold higher risk of having CAD than CC genotype in both SNPs (p = 0.0050 and 0.0192, respectively). DDAH1 rs997251 TC + CC genotypes were associated with 2.3-fold higher risk of CAD than TT genotype (p = 0.0063). Moreover, the AGXT2 rs37369 TT and AGXT2 rs16899974 AA genotypes were associated with the highest serum ADMA and SDMA while DDAH1 rs997251 CC genotype was associated with the highest ADMA. AGXT2 rs37369-T, AGXT2 rs16899974-A, and DDAH1 rs997251-C alleles represent independent risk factors for CAD in the Egyptians. � 2018, Springer Nature B.V.
Description
Scopus
Keywords
Alanine glyoxylate aminotransferase 2, Asymmetric dimethylarginine, Coronary artery disease, Dimethylarginine dimethylaminohydrolase, Nitric oxide, Polymorphisms, Symmetric dimethylarginine, 6 n,n' dimethylarginine, n(g),n(g) dimethylarginine, 6 n,n' dimethylarginine, Alanine-glyoxylate transaminase, amidase, aminotransferase, arginine, dimethylargininase, N,N-dimethylarginine, nitric oxide, adult, AGXT2 gene, allele, Article, cardiovascular risk, controlled study, coronary artery disease, correlation analysis, DDAH 1 gene, Egyptian, enzyme linked immunosorbent assay, female, genetic risk, genetic variability, genotype, human, incidence, major clinical study, male, polymerase chain reaction, quantitative analysis, single nucleotide polymorphism, analogs and derivatives, blood, case control study, coronary artery disease, Egypt, genetic variation, genetics, metabolism, middle aged, Adult, Amidohydrolases, Arginine, Case-Control Studies, Coronary Artery Disease, Egypt, Female, Genetic Variation, Genotype, Humans, Incidence, Male, Middle Aged, Nitric Oxide, Polymorphism, Single Nucleotide, Transaminases