Plasma homocysteine, methylenetetrahydrofolate reductase gene polymorphism and carotid intima‐media thickness in Italian type 2 diabetic patients

Scaglione, L.; Gambino, Roberto; Rolfo, E.; Lillaz, E; Gai, Min-Tao; Cassader, Maurizio; Pagano, Gianfranco; Cavallo‐Perin, P.

doi:10.1046/j.1365-2362.2002.00936.x

Cited by 29 publications

(15 citation statements)

References 20 publications

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“…The increased oxidative stress in subjects with GCPII 1561T variant might be mediated through the elevated homocysteine levels as observed in the current study. These findings are in agreement with other studies in demonstrating increased oxidative stress in CAD cases [19,33].…”

Section: Discussionsupporting

confidence: 94%

“…Hyperhomocysteinemia resulting from aberrations in one-carbon metabolism was demonstrated to increase superoxide anion production by multiple mechanisms [40], includes: (i) inhibition of the activity of cellular antioxidant enzymes such as cellular glutathione peroxidase or hemeoxygenase-1, (ii) homocysteine autooxidation, (iii) NOS-dependent generation of superoxide anion (O 2 -• ) via uncoupling of eNOS, (iv) decrease of extracellular superoxide dismutase activity and (v) by phosphorylation at p47 phox and p67 phox subunits of NADPH oxidase, thereby stimulating superoxide generation [39]. A study found that plasma homocysteine concentration and SNPs in the enzyme MTHFR were not significantly associated with carotid IMT [33]. The most crucial end-product of this pathway i.e., SAM, a universal methyl donor, modulates oxidative stress by potentiating SOD and GST activity and restoring GSH [11].…”

Section: Discussionmentioning

confidence: 99%

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Association of Aberrations in One Carbon Metabolism with Intimal Medial Thickening in Patients with Type 2 Diabetes Mellitus

et al. 2014

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The present work was aimed to study the association of one carbon genetic variants, hyperhomocysteinemia and oxidative stress markers, i.e., serum nitrite, plasma malondialdehyde (MDA) and glutathione (GSH) on intimal medial thickening (IMT) in patients with type 2 diabetes mellitus (T2D). A total number of 76 subjects from ACS Medical College and Hospital, Chennai, India were included in the study, i.e., Group I (n = 42) of T2D and Group II (n = 34) of age- and sex matched healthy controls. The glycated haemoglobin was measured by ion-exchange resin method; plasma homocysteine by Enzyme Linked Immunosorbant Assay method; serum nitrite (nitric oxide, NO), plasma MDA and GSH by spectrophotometric methods; the IMT by high frequency ultrasound. The polymorphisms of one carbon genetic variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism and amplified fragment length polymorphism methods. Results indicate that methyltetrahydrofolate homocysteine methyl transferase (MTR) A2756G allele was found to be protective in T2D and the other variants were not significantly associated with T2D. Glutamate carboxypeptidase II (GCP II) C1561T (r = 0.34; p = 0.05) and methylene tetrahydrofolate reductase (MTHFR) C677T (r = 0.35; 0.04) showed positive correlation with plasma homocysteine in T2D cases. In this study, MTR A2756G allele was found to be protective in T2D; GCP II C1561T and MTHFR C677T showed positive association with plasma homocysteine in T2D cases. Among all the genetic variants, MTR A2756G was found influence IMT. RFC 1 G80A and TYMS 5'-UTR 2R3R showed synergistically interact with MTR A2756G in influencing increase in IMT.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Association of Aberrations in One Carbon Metabolism with Intimal Medial Thickening in Patients with Type 2 Diabetes Mellitus

et al. 2014

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“…We found that the plasma Hcy-lowering effect of the folate supplement was significant in subjects with the 677T allele but not in 677C carriers (Liu et al, 2004). These findings may provide a rational explanation for the inconsistent conclusion of studies of MTHFR C677T-related carotid atherosclerosis (Hamelahti et al, 2002;Scaglione et al, 2002).…”

Section: Discussionmentioning

confidence: 61%

“…In patients with type II diabetes, lower plasma folate concentrations may enhance the tendency for increased plasma Hcy concentrations in subjects with the MTHFR 677TT genotype (Scaglione et al, 2002). Uremic patients with lower concentrations of folate and who were carriers of the MTHFR T allele also had a high incidence of carotid plaque formation and atherosclerotic vascular disease (Haraki et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

B-group vitamins, MTHFR C677T polymorphism and carotid intima-media thickness in clinically healthy subjects

et al. 2007

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Objective: Plasma B-group vitamins and age may affect the carotid intima-media thickness (IMT) in subjects with different 677TT genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. Design: A hospital-based cross-study. Setting: Genomic and Vascular Center, Changhua Christian Hospital, Changhua, Taiwan. Subjects: Five hundred and forty-one clinically healthy subjects. Intervention: Fasting plasma, homocysteine (Hcy), vitamin B 6 , vitamin B 12 , folate and B-mode carotid ultrasound. Results: MTHFR genotype, plasma concentrations of folate, vitamin B 6 and vitamin B 12 and age were significantly correlated to the plasma Hcy concentration. MTHFR 677TT carriers had higher concentrations of Hcy than did subjects with the CC and CT genotypes. Age, sex, body mass index and plasma Hcy were independent contributors to increase carotid IMT. However, with stratification by mean value of age and B-group vitamins concentrations, we found that at advanced age, lower plasma folate and vitamin B 12 were three risk factors involved in the enhancing effect of the MTHFR 677TT genotype on the increase of plasma Hcy and carotid IMT. Conclusion: MTHFR 677TT-related carotid atherosclerosis was only identified in healthy elderly subjects with lower level of plasma folate and vitamin B 12 . Sponsorship: Changhua Christian Hospital.

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“…The association disappeared, however, after adjustment for kidney function. 79 Taken together, most studies found a positive association between homocysteine concentrations and macrovascular disease in individuals with diabetes. Moreover, some studies suggested that homocysteine may be a stronger risk factor among individuals with than without diabetes.…”

Section: Figmentioning

confidence: 98%

Epidemiology of Homocysteine as a Risk Factor in Diabetes

Becker

Smulders²,

Guldener³

et al. 2003

Metabolic Syndrome and Related Disorders

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Patients with diabetes mellitus are prone to cardiovascular disease, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinemia, may be involved in the atherothrombotic process in these subjects. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. This has been ascribed to hyperfiltration and renal dysfunction or low folate status, respectively. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration has also been shown to be related to macrovascular disease and death. This relation seems to be stronger in subjects with diabetes than without. The underlying pathophysiological mechanism of this increased vascular risk remains unexplained, but may relate to worsening of endothelial dysfunction or structural vessel properties. Because homocysteine and diabetes have an apparent synergistic detrimental vascular effect, patients with diabetes are good candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.

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Plasma homocysteine, methylenetetrahydrofolate reductase gene polymorphism and carotid intima‐media thickness in Italian type 2 diabetic patients

Abstract: In 124 Italian patients with type 2 diabetes mellitus, basal levels of plasma homocysteine, as well as methylenetetrahydrofolate reductase gene polymorphism, did not explain the variability of mean carotid intima-media thickness.

Cited by 29 publications

References 20 publications

Association of Aberrations in One Carbon Metabolism with Intimal Medial Thickening in Patients with Type 2 Diabetes Mellitus

Association of Aberrations in One Carbon Metabolism with Intimal Medial Thickening in Patients with Type 2 Diabetes Mellitus

B-group vitamins, MTHFR C677T polymorphism and carotid intima-media thickness in clinically healthy subjects

Epidemiology of Homocysteine as a Risk Factor in Diabetes

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