Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis

Theodoros Dimitroulas; Aamer Sandoo; James Hodson; Jacqueline Smith; Vasileios F. Panoulas; George D. Kitas

doi:10.1016/j.atherosclerosis.2014.07.033

Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis

Theodoros Dimitroulas, Aamer Sandoo, James Hodson, Jacqueline Smith, Vasileios F. Panoulas, George D. Kitas

Birmingham Medical School

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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.

Original language	English
Pages (from-to)	38-44
Journal	Atherosclerosis
Volume	237
Issue number	1
Early online date	27 Aug 2014
DOIs	https://doi.org/10.1016/j.atherosclerosis.2014.07.033
Publication status	Published - 1 Nov 2014

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10.1016/j.atherosclerosis.2014.07.033

Sandoo_Gene_variants_asymmetric_dimethylarginine_Atherosclerosis_2014
NOTICE: this is the author’s version of a work that was accepted for publication in Atherosclerosis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Atherosclerosis, Vol 237, Issue 1, November 2014 DOI: 10.1016/j.atherosclerosis.2014.07.033 Eligibility for repository checked
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Centre for Musculoskeletal Ageing Research (linked to 18289 & 19482)
Lord, J., Buckley, C., Duda, J., Dunn, W., Miall, C. & Greig, C.
Medical Research Council
1/08/12 → 31/07/17
Project: Research Councils

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@article{e9a5c3e354c14ca696f526da1d026b82,

title = "Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis",

abstract = "ObjectiveThe 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).MethodsSerum 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{\texttrademark} 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.ResultsNo 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.ConclusionThe 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.",

author = "Theodoros Dimitroulas and Aamer Sandoo and James Hodson and Jacqueline Smith and Panoulas, {Vasileios F.} and Kitas, {George D.}",

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doi = "10.1016/j.atherosclerosis.2014.07.033",

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volume = "237",

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T1 - Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis

AU - Dimitroulas, Theodoros

AU - Sandoo, Aamer

AU - Hodson, James

AU - Smith, Jacqueline

AU - Panoulas, Vasileios F.

AU - Kitas, George D.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - ObjectiveThe 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).MethodsSerum 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.ResultsNo 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.ConclusionThe 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.

AB - ObjectiveThe 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).MethodsSerum 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.ResultsNo 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.ConclusionThe 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.

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DO - 10.1016/j.atherosclerosis.2014.07.033

M3 - Article

SN - 0021-9150

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SP - 38

EP - 44

JO - Atherosclerosis

JF - Atherosclerosis

IS - 1

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Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis

Abstract

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