title: Missense variants of the alanine: glyoxylate aminotransferase 2 gene correlated with carotid atherosclerosis in the Japanese population.
abstract: Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice. There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and rs16899974) with which AGXT2 activity changes in humans and may be related to vulnerability of vascular sclerosis. To examine the relationship between them, we studied the functional haplotypes of the AGXT2 gene and decided their relationship with arteriosclerotic changes via carotid intima-media thickness (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity (P<0.0001; Pearsons correlation coefficients: 0.497). The C-A-A-A haplotype was significantly associated with mean carotid IMT (P=0.049) and max carotid IMT (P=0.004). Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid IMT (P=0.022) and maximum carotid IMT (P=0.001). In multiple regression analysis, subjects with two C-A-A-A haplotypes were independently and positively associated with mean carotid IMT (P=0.02) and maximum IMT (P=0.005) after correction. There was a significant correlation between the functional variants in the AGXT2 gene and carotid IMT in Japanese. The AGXT2 genotype may be an important factor underlying atherosclerosis.
authors.affiliation: Department of Neuropsychiatry, Molecule and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshino
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kohara
authors.affiliation: Department of Neuropsychiatry, Molecule and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Neuropsychiatry, Molecule and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ochi
authors.affiliation: Department of Neuropsychiatry, Molecule and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Neuropsychiatry, Molecule and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Igase
authors.affiliation: Department of Clinical Genetics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tabara
authors.affiliation: Department of Neuropsychiatry, Molecule and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Neuropsychiatry, Molecule and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000328:Adult; D000368:Aged; D002340:Carotid Artery Diseases / Q000209:etiology / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000637:Transaminases / Q000235:genetics*
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase