title: Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study.
abstract: The role of hyperhomocysteinemia as a risk factor for diabetic long-term complications has not been sufficiently evaluated in prospective studies, considering specific correlates of homocysteine (tHcy) concentration and traditional cardiovascular disease (CVD) risk factors. Fasting tHcy, vitamin B12 and folate plasma levels, the common methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, as well as clinical and lifestyle information were assessed in 216 type 2 diabetic patients attending two outpatient clinics, who had a follow-up evaluation at 65 ± 9 months for the incidence of macroangiopathy. At basal evaluation, mild hyperhomocysteinemia (tHcy ≥ 15 μmol/l) was diagnosed in 21.3% of participants. At follow-up, hyperhomocysteinemia and the distribution of MTHFR C677T genotype did not significantly differ according to the incidence of macroangiopathy. Multiple variables adjusted ORs (95% CI) for CVD associated with mild hyperhomocysteinemia were 1.01 (0.37-2.82); P > 0.05; those associated with MTHFR TT genotype were 0.46 (0.15-1.38); P > 0.05. Although the prevalence of hyperhomocysteinemia was higher in diabetic men (26.9%) than in women (16.1%; P > 0.05), similar results were also observed in a separate sex-analysis. At the multivariate analysis, including in the model other potential CVD risk factors, only creatinine clearance was a significant risk factor for the development of macroangiopathy. In this cohort of diabetic subjects, mild hyperhomocysteinemia and the MTHFR TT genotype are not significant risk factors for the development of macroangiopathy; impaired renal function was confirmed as a significant predictor of this complication.
authors: Department of Internal Medicine, Policlinico Universitario "G. Martino" Via C. Valeria, University of Messina, Italy. giuseppina.russo@unime.it
authors: Giuseppina Tiziana
authors: GT
authors: Russo
authors: Antonino
authors: A
authors: Di Benedetto
authors: Domenico
authors: D
authors: Magazzù
authors: Annalisa
authors: A
authors: Giandalia
authors: Carlo Bruno
authors: CB
authors: Giorda
authors: Riccardo
authors: R
authors: Ientile
authors: Marcello
authors: M
authors: Previti
authors: Enrico
authors: E
authors: Di Cesare
authors: Domenico
authors: D
authors: Cucinotta
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)