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AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA levels and with incidence of coronary artery disease in Egyptians

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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.

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Authors and Affiliations

  1. Clinical Biochemistry Unit, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Main Entrance El-Tagamoa El-Khames, New Cairo City, Cairo, Egypt

    Mina Amir, Sally I. Hassanein & Mohamed Z. Gad

  2. Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Cairo, Egypt

    Mohamed F. Abdel Rahman

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  1. Mina Amir
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  2. Sally I. Hassanein
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  3. Mohamed F. Abdel Rahman
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  4. Mohamed Z. Gad
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Contributions

Concept—MZG, SIH; design—MZG, SIH, MA; supervision—MZG, SIH; fundings—MZG, SIH; materials—HAS; data collection and/or processing—MA, SIH; analysis and/or interpretation—MZG, SIH, MFA, MA; literature review—MA, MFA; writing—MZG, SIH, MFA, MA; critical review—MZG.

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Correspondence to Sally I. Hassanein.

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German University Cairo ethics committee [Chair of Committee Prof. Dr. Hans-Georg Breitinger, Hans-Georg Breitinger (hans.breitinger@guc.edu.eg)], approved the study protocols.

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Amir, M., Hassanein, S.I., Abdel Rahman, M.F. et al. AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA levels and with incidence of coronary artery disease in Egyptians. Mol Biol Rep 45, 2411–2419 (2018). https://doi.org/10.1007/s11033-018-4407-1

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