title: Homocysteine, folate, methylene tetrahydrofolate reductase genotype and vascular morbidity in diabetic subjects.
abstract: 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.
authors.affiliation: Department of Endocrinology and Diabetes, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia, Australia.
authors.forename: Joey M
authors.initials: JM
authors.lastname: Kaye
authors.forename: Kim G
authors.initials: KG
authors.lastname: Stanton
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: McCann
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Vasikaran
authors.forename: Valerie
authors.initials: V
authors.lastname: Burke
authors.forename: Roger R
authors.initials: RR
authors.lastname: Taylor
authors.forename: Frank M
authors.initials: FM
authors.lastname: van Bockxmeer
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003327:Coronary Disease / Q000097:blood; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D003925:Diabetic Angiopathies / Q000097:blood* / Q000235:genetics; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D020521:Stroke / Q000097:blood
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)