Abstract | OBJECTIVE: RESEARCH DESIGN AND METHODS: Prevalent CVD was assessed in men and women aged 60-75 years with type 2 diabetes as part of the Edinburgh Type 2 Diabetes Study (ET2DS), and the participants were prospectively followed up for 4 years for incident CVD. Dimethylarginines were measured in 783 of these subjects, and genotyping for tag SNPs in the DDAH1, DDAH2, and AGXT2 genes was performed in 935 subjects. RESULTS: Plasma ADMA levels were significantly associated with SNPs in DDAH1 (top SNP rs1554597; P = 9.0E-09), while SDMA levels were associated with SNPs in AGXT2 (top SNP rs28305; P = 1.3E-04). Significant, independent determinants of plasma ADMA were sex, L-arginine, creatinine, fasting glucose, and rs1554597 (all P < 0.05; combined R(2) = 0.213). Determinants of SDMA were age, sex, creatinine, L-arginine, diabetes duration, prevalent CVD, and rs28305 (all P < 0.05; combined R(2) = 0.425). Neither dimethylarginine was associated with incident CVD. None of the investigated SNPs were associated with overall CVD, although subgroup analysis revealed a significant association of AGXT2 rs28305 with intermittent claudication. CONCLUSIONS: Our study in a well-characterized population with type 2 diabetes does not support reported associations or causal relationship between ADMA and features of diabetes or CVD.
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Authors | Maike Anderssohn, Stela McLachlan, Nicole Lüneburg, Christine Robertson, Edzard Schwedhelm, Rachel M Williamson, Mark W J Strachan, Ramzi Ajjan, Peter J Grant, Rainer H Böger, Jackie F Price |
Journal | Diabetes care
(Diabetes Care)
Vol. 37
Issue 3
Pg. 846-54
( 2014)
ISSN: 1935-5548 [Electronic] United States |
PMID | 24186881
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- dimethylarginine
- symmetric dimethylarginine
- N,N-dimethylarginine
- Arginine
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Topics |
- Aged
- Arginine
(analogs & derivatives, blood, genetics)
- Cardiovascular Diseases
(blood, epidemiology)
- Diabetes Mellitus, Type 2
(blood, epidemiology, genetics)
- Diabetic Angiopathies
(epidemiology, etiology)
- Environment
- Female
- Genotype
- Humans
- Intermittent Claudication
(epidemiology, genetics)
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Risk Factors
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