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Abstract

We assessed the contribution of serum homocysteine levels, an independent risk factor for vascular disease, and of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation to the variability of carotid intimal-medial thickness (IMT) in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ninety-five patients (33 males and 62 females, mean age 53 +/- 10 years) without nephropathy or other vascular complications were enrolled. Fasting total serum homocysteine and other biochemical analytes were measured. The MTHFR polymorphism was determined by the polymerase chain reaction. Common carotid IMT and plaques or stenoses in the carotid district were measured by ultrasonography. Serum total homocysteine concentrations were higher in subjects with the mutant (Val/Val) genotype than in those with the Ala/Val plus Ala/Ala genotypes (P = 0.02). On univariate analysis, carotid IMT was significantly associated with age, body mass index (BMI), systolic blood pressure, and total cholesterolemia. No significant association was found between IMT and serum homocysteine or the MTHFR polymorphism, although a slightly greater IMT was observed in the homozygous Val genotypes. On multiple regression analysis, only age and BMI were independently associated with IMT and explained about 40% of IMT variability. The results did not change when the analysis was restricted to the subgroups with or without atherosclerotic plaques in the carotid district. In 95 Italian NIDDM patients without nephropathy, neither basal levels of serum total homocysteine nor the MTHFR C677T polymorphism predicted significant changes in common carotid intimal-medial thickness.

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

“…The frequencies of the CC genotype were the highest in controls and in cases, while that for genotype TT was the lowest. Three studies only reported the association between blood Hcy level and MTHFR 677 C > T in diabetes patients [48-50]. In three studies [34-36], the distribution of the genotypes in the control group was not in HWE (p < 0.05) (Table 1).…”

“…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.…”

Does the MTHFR C677T gene polymorphism indicate cardiovascular disease risk in type 2 diabetes mellitus patients?

“…In addition, in individuals with thicker cIMTs, the risk of stroke and coronary artery disease is known to be higher (1, 47, 48). It was shown that although there was a notable correlation between cIMT and BMI, age, SBP and total cholesterolemia, there was no correlation between cIMT and serum homocysteine and MTHFR gene polymorphisms in nephropathy-free T2DM patients (49). In our study, while cIMT values depended significantly on age (p<0.001) and BMI (p=0.05), there were no meaningful correlations between cIMT values and MTHFR C677T polymorphism, SBP DBP LDL and HDL-cholesterol, and triglyceride values.…”