Theodoros Dimitroulas1, Aamer Sandoo2, James Hodson3, Jacqueline Smith4, Vasileios F Panoulas5, George D Kitas6. 1. Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK. Electronic address: dimitroul@hotmail.com. 2. Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK; School of Sport, Health and Exercise Sciences, Bangor University, George Building, Bangor, Gwynedd, Wales LL57 2PZ, UK. 3. Wolfson Computer Laboratory, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham B15 2WB, UK. 4. Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK. 5. National Heart and Lung Institute, Imperial College London, UK. 6. Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK; Arthritis Research UK Epidemiology Unit, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Abstract
OBJECTIVE: The aim of our study was to determine whether Dimethylarginine Dimethylaminohydrolase (DDAH) 1 and 2 gene polymorphisms - the main enzyme involved in ADMA degradation - are associated with high Asymmetric Dimethylarginine (ADMA) levels in Rheumatoid Arthritis (RA). METHODS: Serum ADMA levels were measured in 201 individuals with RA [155 females median age 67 (59-73)]. Four tag SNPs in DDAH1 gene and 2 in the DDAH2 gene were genotyped by using the LightCycler™ System. ADMA was initially compared across the genetic variables using one-way ANOVA and then multivariate analysis examined each of the genes after adjustment for parameters of systemic inflammation and insulin resistance, namely erythrocyte sedimentation rate (ESR) and homeostatic model assessment (HOMA), which we have previously shown affect ADMA levels in RA. RESULTS: No significant relationship between DDAH genetic variables and ADMA levels was established in ANOVA analysis. Multivariate model adjusted for age, HOMA and ESR did not demonstrate any significant association between DDAH variants and ADMA. CONCLUSION: The results of our study give no evidence to suggest that increased ADMA levels in RA relate to DDAH genetic polymorphisms. Better understanding of disease-related factors and their interactions with traditional CV risk factors may represent mechanisms responsible for ADMA accumulation in this population.
OBJECTIVE: The aim of our study was to determine whether Dimethylarginine Dimethylaminohydrolase (DDAH) 1 and 2 gene polymorphisms - the main enzyme involved in ADMA degradation - are associated with high Asymmetric Dimethylarginine (ADMA) levels in Rheumatoid Arthritis (RA). METHODS: Serum ADMA levels were measured in 201 individuals with RA [155 females median age 67 (59-73)]. Four tag SNPs in DDAH1 gene and 2 in the DDAH2 gene were genotyped by using the LightCycler™ System. ADMA was initially compared across the genetic variables using one-way ANOVA and then multivariate analysis examined each of the genes after adjustment for parameters of systemic inflammation and insulin resistance, namely erythrocyte sedimentation rate (ESR) and homeostatic model assessment (HOMA), which we have previously shown affect ADMA levels in RA. RESULTS: No significant relationship between DDAH genetic variables and ADMA levels was established in ANOVA analysis. Multivariate model adjusted for age, HOMA and ESR did not demonstrate any significant association between DDAH variants and ADMA. CONCLUSION: The results of our study give no evidence to suggest that increased ADMA levels in RA relate to DDAH genetic polymorphisms. Better understanding of disease-related factors and their interactions with traditional CV risk factors may represent mechanisms responsible for ADMA accumulation in this population.
Authors: László Dávida; Vanda Pongrácz; Emir Awad Mohamed; Szilvia Szamosi; Gabriella Szücs; Andrea Váncsa; Orsolya Tímár; Zoltán Csiki; Edit Végh; Pál Soltész; Zoltán Szekanecz; György Kerekes Journal: Rheumatol Int Date: 2019-12-19 Impact factor: 2.631