Plasma Total Homocysteine Levels and Methylenetetrahydrofolate Reductase Gene Polymorphism in Patients with Type 2 Diabetes Mellitus

Abstract

Background: Thrombotic episodes account for approximately 80% of deaths in type 2 diabetic patients. Hyperhomocysteinaemia is a well recognized independent risk factor for atherosclerosis and thromboembolism. Increased homocysteine levels may occur due to a number of factors including inherited gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T. Here, we evaluate plas- ma total homocysteine (tHcy) levels and frequency of the MTHFR C677T gene polymorphism in asymptomatic healthy volunteers and type 2 diabetic patients with hypertension but without nephropathy. We have also investigated the relationship between tHcy levels and the presence of MTHFR C677T gene polymorphism. Methods: Plasma tHcy levels and MTHFR C677T genotype were investigated in a total of 53 subjects. These included asymptomatic healthy volunteers (n = 16), patients with type 2 diabetes (n = 7), subjects with hypertension (n = 12) and patients with both type 2 diabetes and hypertension (n = 18). Renal function, serum lipids and other metabolites were also assessed. Results: There was no significant difference in tHcy levels between the groups studied. The frequency of MTHFR C677T gene polymorphism observed was similar to that obtained for the general Brazilian population. In patients with type 2 diabetes and hypertension but without impaired renal function, we observed no meaningful correlation between increased tHcy levels and the presence of MTHFR C677T gene polymorphism. Conclusions: Type 2 diabetics who are homozygous or heterozygous for the MTHFR C677T gene polymorphism showed normal tHcy levels. Our results further suggest that diabetes without an associated adverse risk profile is not an independent correlate of increased tHcy levels.

Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach

“…Eleven studies (2498 T2DM) [ 12 , 25 , 30 , 31 , 35 , 38 , 39 , 48 - 50 ] were identified that satisfied inclusion criteria and expressed the between-group difference in plasma Hcy level in terms of the arithmetic mean and standard deviation. In all these studies, the mean Hcy concentration was greater in subjects with MTHFR 677TT than in those with the other two genotypes.…”

Methylenetetrahydrofolate Reductase Gene Polymorphism and Risk of Type 2 Diabetes Mellitus

“…A meta-analysis published in 1998 concluded there was an association between the TT genotype and elevated plasma homocysteine levels in individuals with T2DM [17], while a more recent prospective study found no such association [72]. Thus, we second the conclusions of previous authors that the link between Hcy levels and T2DM remains unclear [48], [53], [56], [60]. The recommendation of the College of American Pathologists to measure Hcy only in patients with documented atherosclerotic disease [73] seems reasonable, given that HHcy is commonly accepted to be an independent risk factor for atherosclerosis and thromboembolism [74].…”

“…Most of the studies included in the present systematic review did not analyze Hcy levels in cases and controls, making it difficult to gain a comprehensive picture. Of the studies that did examine whether Hcy levels were associated with the rs1801133 polymorphism, 11 found the TT genotype to be associated with higher Hcy levels than the CT or CC genotypes in patients with T2DM [7], [8], [31], [32], [35], [45], [46], [51], [54], [59], [60], while 6 found no such association [27], [48], [49], [52], [56], [57]. A meta-analysis published in 1998 concluded there was an association between the TT genotype and elevated plasma homocysteine levels in individuals with T2DM [17], while a more recent prospective study found no such association [72].…”

Association of MTHFR C677T polymorphism and type 2 diabetes mellitus (T2DM) susceptibility

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