Журнал ишемической болезни сердца

AGXT2 and DDAH-1 Genetic Variants are Highly Correlated with Serum ADMA and SDMA Levels and with Incidence of Coronary Artery Disease in Egyptians

Abstract

Mina Amir , Sally I Hassanein, Mohamed F Abdel Rahman and Mohamed Z Gad

Background: Dimethylarginine aminodehydrolase (DDAH1) and alanine glyoxylate aminotransferase2 (AGXT2) are two enzymes that contribute in the asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) metabolism. ADMA and SDMA are two known endogenous arginine derivatives reported to affect the 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 the genetic variants of AGXT2 rs37369, AGXT2 rs16899974 and DDAH1 rs997251 SNPs with the incidence of coronary artery disease (CAD) in the Egyptian population and to correlate these variants with the serum levels of ADMA and SDMA.
Methods: 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.
Results: 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 genotype, AGXT2 rs16899974 AA genotype and DDAH1 rs997251 CC genotype were associated with the highest serum ADMA and SDMA concentrations.
Conclusion: AGXT2 rs37369-T, AGXT2 rs16899974-A, and DDAH1 rs997251-C alleles represent independent risk factors for CAD in the Egyptians.