Authors: Ciccarone E.; Di Castelnuovo A.¹; Assanelli D.²; Archetti S.³; Ruggeri G.³; Salcuni N.⁴; Donati M.B.⁵; Capani F.⁶; Iacoviello L.¹

Source: Journal of Thrombosis and Haemostasis, Volume 1, Number 12, December 2003 , pp. 2540-2547(8)

Publisher: Wiley-Blackwell

Abstract:

Summary.

Background: Homocysteine levels are positively associated with the risk of cardiovascular disease. They might be determined by both MTHFR677CT polymorphisms and folate or B-vitamin status. Objectives: To investigate the possible association between plasma homocysteine levels and its genetic or environmental determinants and either the presence or the severity of peripheral arterial disease (PAD), in Type 2 diabetic patients. Methods: From a cohort of 944 patients with Type 2 diabetes, 135 patients with PAD were selected, and frequency-matched for age and sex with 219 Type 2 diabetic control patients without macrovascular complications. According to the increasing severity of the disease, patients were divided into PAD₁ (only diffuse calcifications of the arteries without any stenosis or occlusion), PAD₂ (one or two stenosis or occlusions) and PAD₃ (three or more). Results: Homocysteine levels were similar in control and case patients (10.3 µmol L^-1 vs. 10.7 µmol L^-1, P = 0.53); however, a significant increase was found in PAD₃ patients: odds ratio = 2.77 (95% confidence interval 1.14, 6.72) for patients with homocysteine levels above the median vs. those under the median in multivariate analysis. Although all significantly associated with homocysteine levels, neither MTHFR genotype nor folic acid or vitamin B₁₂ levels were associated with severity of PAD. A significant interaction (P < 0.05) was found between folic acid and MTHFR polymorphism in determining the levels of homocysteine. Conclusions: In Type 2 diabetes, homocysteine was associated with the angiographic severity of PAD, but neither the genotypes nor vitamin levels contributed to this association.

Keywords: homocysteine; MTHFR polymorphism; peripheral arterial disease; Type 2 diabetes

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1538-7836.2003.00500.x

Affiliations: 1: ‘Angela Valenti’ Laboratory of Genetic and Environmental Risk Factors for Thrombotic Disease, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 2: Chair of Cardiology, University of Brescia and 3: 3rd Laboratory, Spedali Civili, Brescia, Italy; and 4: Institute of Radiology, University of Chieti, Chieti, Italy; 5: Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy 6: Department of Medicine and Aging and

Publication date: 2003-12-01

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