title: Genetic variations in the alanine-glyoxylate aminotransferase 2 (AGXT2) gene and dimethylarginines levels in rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is associated with high rates of cardiovascular events mainly due to coronary and cerebrovascular atherosclerotic disease. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines are endogenous inhibitors of nitric oxide synthase and have been repeatedly linked with adverse cardiovascular outcomes in the general population and various disease settings. Alanine-glyoxylate aminotransferase 2 (AGTX2) is considered an alternative metabolic pathway contributing to the clearance of dimethylarginines in humans. The aim of the current study was to investigate the effect of specific AGXT-2 gene polymorphisms on circulating levels of ADMA or SDMA in patients with RA. Serum ADMA and SDMA levels were measured in 201 individuals with RA [median age: 67 years (IQR: 59-73), 155 females]. Two single nucleotide polymorphisms (SNPs) in the AGXT-2 gene-rs37369 and rs28305-were genotyped. Distributions of SDMA and ADMA were skewed, hence comparisons across the gene polymorphisms were performed using Kruskal-Wallis tests, and summarized using medians and interquartile ranges. Univariable analysis did not demonstrate a significant difference in the levels of SDMA or ADMA amongst the different genotypic groups of either rs37369AGXT2 (p = 0.800, 0.977) or rs28305AGXT2 (p = 0.463, 0.634). In multivariable analyses, ADMA levels were found to be significantly associated with erythrocyte sedimentation rate and estimated glomerular filtration rate, whilst SDMA levels were significantly associated with estimated glomerular filtration rate and quantitative insulin sensitivity check index. After adjustments for these factors, the relationship between the AGXT2 gene variants and both ADMA and SDMA remained non-significant. Our study in a well-characterized RA population did not show an association between serum concentrations of dimethylarginines and genetic variants of the AGXT2 gene.
authors.affiliation: Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS FT, Dudley, UK. dimitroul@hotmail.com.|4th Department of Internal Medicine, School of Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Street, 54642, Thessaloniki, Greece. dimitroul@hotmail.com.
authors.forename: Theodoros
authors.identifier: 0000-0002-0364-1642
authors.initials: T
authors.lastname: Dimitroulas
authors.affiliation: Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Foundation Trust, Mindelsohn Way, Birmingham, B15 2WB, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hodson
authors.affiliation: Cardiovascular Sciences, Imperial College London, National Heart and Lung Institute, London, UK.
authors.forename: Vasileios F
authors.initials: VF
authors.lastname: Panoulas
authors.affiliation: Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS FT, Dudley, UK.|School of Sport, Health and Exercise Sciences, Bangor University, George Building, Bangor, Gwynedd, LL57 2PZ, Wales, UK.
authors.forename: Aamer
authors.initials: A
authors.lastname: Sandoo
authors.affiliation: Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS FT, Dudley, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Smith
authors.affiliation: Arthritis Research UK Epidemiology Unit, University of Manchester, Oxford Road, Manchester, UK.
authors.forename: George
authors.initials: G
authors.lastname: Kitas
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000637:Transaminases / Q000235:genetics*
chemical_list: C487735:dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase
keywords: ADMA; AGTX2; Atherosclerosis; Rheumatoid arthritis; SDMA