In the present study, the determinants of fasting plasma homocysteine in diabetic subjects were examined; whether plasma homocysteine and vascular disease are related and the influence of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene on serum and erythrocyte folate, plasma homocysteine and vascular disease. Diabetic clinic subjects (Type I, n = 354; Type II, n = 392) were recalled for a cross-sectional survey. Standard methods were used to measure biochemical variables and to characterize vascular disease and MTHFR genotype. Plasma homocysteine was significantly and directly related to age, male sex and serum urea, and inversely related to serum folate and vitamin B12, independently in stepwise regression. When corrected for age and sex, homocysteine was significantly related to hard end points of coronary artery disease and stroke (each P<0.01), remaining significant when additionally adjusted for serum folate (P = 0.043 and P = 0.019 respectively). Serum folate was not clearly related to these events, although there was a trend to associate with the lower quintile of serum folate. The MTHFR genotype was not a determinant of plasma homocysteine, even in those in the lowest quintile of serum folate, nor of vascular disease. TT homozygosity at residue 677 was associated with elevation of total erythrocyte folate compared with both other genotypes (P<0.0001), almost certainly due to the diversion of 5,10-methylenetetrahydrofolate into derivates subsequent to the partial metabolic block that results from the MTHFR enzyme defect. In conclusion, in this clinic cohort of people with diabetes, vascular disease is related to plasma homocysteine, which is correlated with serum folate. The MTHFR genotype does not significantly influence either plasma homocysteine or vascular disease, despite it being a determinant of erythrocyte folate, which reflects its effect on folate metabolism.
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May 17 2002
Homocysteine, folate, methylene tetrahydrofolate reductase genotype and vascular morbidity in diabetic subjects
Joey M. KAYE;
Joey M. KAYE
*Department of Endocrinology and Diabetes, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
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Kim G. STANTON;
Kim G. STANTON
*Department of Endocrinology and Diabetes, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
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Vincent J. MCCANN;
Vincent J. MCCANN
*Department of Endocrinology and Diabetes, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
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Samuel D. VASIKARAN;
Samuel D. VASIKARAN
†Department of Biochemistry, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
‡Department of Pathology, The University of Western Australia, Nedlands 6907, Western Australia, Australia
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Valerie BURKE;
Valerie BURKE
§The University of Western Australia Department of Medicine, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
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Roger R. TAYLOR;
Roger R. TAYLOR
§The University of Western Australia Department of Medicine, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
ǁDepartment of Cardiology, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
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Frank M. VAN BOCKXMEER
†Department of Biochemistry, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia
‡Department of Pathology, The University of Western Australia, Nedlands 6907, Western Australia, Australia
Correspondence: Professor Frank M. van Bockxmeer (e-mail [email protected])
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Publisher: Portland Press Ltd
Received:
November 06 2001
Revision Received:
January 22 2002
Accepted:
February 27 2002
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 102 (6): 631–637.
Article history
Received:
November 06 2001
Revision Received:
January 22 2002
Accepted:
February 27 2002
Citation
Joey M. KAYE, Kim G. STANTON, Vincent J. MCCANN, Samuel D. VASIKARAN, Valerie BURKE, Roger R. TAYLOR, Frank M. VAN BOCKXMEER; Homocysteine, folate, methylene tetrahydrofolate reductase genotype and vascular morbidity in diabetic subjects. Clin Sci (Lond) 1 June 2002; 102 (6): 631–637. doi: https://doi.org/10.1042/cs1020631
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