Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method

• Published in: BMC genomics Vol. 22; no. 1; p. 287
• Main Authors: Yoshino, Yuta, Kumon, Hiroshi, Mori, Takaaki, Yoshida, Taku, Tachibana, Ayumi, Shimizu, Hideaki, Iga, Jun-Ichi, Ueno, Shu-Ichi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.04.2021; BioMed Central; BMC
• Subjects: ADMA; Aged; AGXT2; Alanine; Amidohydrolases - genetics; Arginine; Atherosclerosis; Blood Glucose; Blood pressure; Blood Pressure - genetics; Blood sugar; Cardiovascular disease; Cardiovascular diseases; Casual blood sugar; Diabetes mellitus; Dimethylargininase; Enumeration; Enzymatic activity; Enzymes; Equilibrium; Gene deletion; Genetic aspects; Genomics; Haplotypes; Health aspects; Humans; Hypertension; Insertion; Japan; Kidney diseases; Medical research; Medicine, Experimental; Metabolites; Multiple regression analysis; Nitric oxide; Nitric-oxide synthase; Nucleotides; Plasma; Polls & surveys; Polymorphism; Polymorphism, Single Nucleotide; Regression analysis; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Surveys and Questionnaires; Thymine; Transaminases - genetics; Transferases; Variance analysis; Vascular diseases; Japan; Casual blood sugar; ADMA; Blood pressure; AGXT2
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-021-07612-3

Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) is the only enzyme that degrades the R-form of 3-aminoisobutyrate, an intermediate metabolite of thymine. AGXT2, as well as diaminoarginine dimethylaminohydrolase 1 (DDAH1; EC 3.5.3.18), works as an enzyme that degrades asymmetric dimethylarginine (ADMA), which competitively inhibits the nitric oxide synthase family. Thus, these two enzyme activities may change vascular vulnerability for a lifetime via the nitric oxide (NO) system. We investigated the association between vascular conditions and diseases such as hypertension and diabetes mellitus and polymorphisms of these two genes in 750 older Japanese subjects (mean age ± standard deviation, 77.0 ± 7.6 years) recruited using the complete enumeration survey method in the Nakayama study. Demographic and biochemical data, such as blood pressure (BP) and casual blood sugar (CBS), were obtained. Four functional single nucleotide polymorphisms (SNPs; rs37370, rs37369, rs180749, and rs16899974) of AGXT2 and one functional insertion/deletion polymorphism in the promotor region with four SNPs (rs307894, rs669173, rs997251, and rs13373844) of DDAH1 were investigated. Plasma ADMA was also analyzed in 163 subjects. The results of multiple regression analysis showed that a loss of the functional haplotype of AGXT2, CAAA, was significantly positively correlated with BP (systolic BP, p = 0.034; diastolic BP, p = 0.025) and CBS (p = 0.021). No correlation was observed between DDAH1 and either BP or CBS. ADMA concentrations were significantly elevated in subjects with two CAAA haplotypes compared with subjects without the CAAA haplotype (p = 0.033). Missense variants of AGXT2, but not DDAH1, may be related to vulnerability to vascular diseases such as hypertension and DM via the NO system.