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Background/aim: Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil., Method: One hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week., Results: Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the MTHFR genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03)., Conclusion: Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.

Peripheral arterial disease (PAD) is an atherosclerotic disturbance characterized by a progressive obstruction of lower limb arteries. Many risk factors associated with PAD development have being reported in the literature. The present study aimed to investigate whether mutations in the methylenetetrahydrofolate reductase (MTHFR) or in the cystathionine beta synthase (CBS) genes are associated with higher levels of homocysteine and the risk of PAD in patients from Brazil. This study analyzed 39 patients with PAD and 32 without PAD in whom risk factors and C677T mutations in the MTHFR gene and both 844ins68 and T833C mutations in the CBS gene were investigated. Although higher levels of homocysteine could be observed in patients with PAD compared to controls, no association between the increase of homocysteine and the frequency of C677T, 844ins68, and T833C mutations could be observed. The results suggest that these mutations do not appear to be related to either homocysteine levels or the development of the disease. However, hyperhomocysteinemia and smoking are important factors in PAD development.

This study aimed to compare plasma levels of total homocysteine (tHcy) in different arterial events as well as to investigate an association between homocysteine levels and C677T polymorphism in Brazilian patients. A total of 145 subjects were enrolled in this study including 43 patients with coronary arterial disease (CAD), 21 with ischemic stroke (IS), 44 with peripheral arterial obstructive disease (PAOD) and 37 control subjects. A preliminary analysis showed significant difference for tHcy plasma levels between patients with CAD (P = 0.003) or PAOD (P = 0.03) compared to controls. However, after adjustment for sex, age, total cholesterol, LDL, diabetes, tabagism or C677T polymorphism, no significant differences were detected in tHcy levels among patients groups and controls. No significant correlation was demonstrated for C677T polymorphism and homocysteine levels. These results indicate that increased Hcy levels may not be considered an independent risk factor for atherothrombotic diseases in Brazilian patients.

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., (Copyright 2009 S. Karger AG, Basel.)

Hyperhomocysteinemia is associated with increased coronary artery disease (CAD) risk. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of homocysteine and presents a common mutation (C677T) that leads to a thermolabile enzyme, mild hyperhomocysteinemia, and increased CAD risk. The C677T MTHFR mutation was studied in 772 subjects (480 Caucasian Brazilians and 292 African Brazilians) who underwent coronary angiography at the hemodynamic center of the Santa Izabel Hospital in Salvador, Bahia State, Brazil. The 677T allele frequency was increased in Caucasian Brazilians (28.1%) compared to the frequency observed in African Brazilians (18.3%; p < 0.001). In Caucasian Brazilians the frequency of the 677T homozygous genotype was increased in CAD cases (10.4%) compared to control subjects (1.4%; p = 0.014) in males but not in females. In African Brazilians the mutation was not associated with CAD in either sex. The multivariate logistic regression analysis of all the samples shows that the 677T homozygous interaction with sex was a significant CAD predictor, independent of other classical risk factors and ethnic group. The odds ratio associated with male 677T homozygotes was increased 9.2-fold (p = 0.021) compared to the 677C carriers. The present study suggests that the C677T MTHFR mutation is associated with increased CAD risk in a sex-dependent manner in Brazilians.

One of the etiologies of hyperhomocysteinemia is decreased vitamin B(12). Genetic variation in the transcobalamin II gene, the transporter of vitamin B(12) to the cells, may produce altered homocysteine levels. We determined transcobalamin II C776G polymorphism, homocysteine, folate and vitamin B(12) levels and analyzed the interactive effect with the methylenetetrahydrofolate reductase C677T and A1298C and methionine synthase reductase A66G polymorphisms in 207 healthy Brazilian children. The prevalence of GG genotype of transcobalamin II C776G polymorphism in this Brazilian population, a highly miscigeneous population was 12.5% and the statistical analysis showed that this population is in Hardy-Weinberg equilibrium, it could be considered representative of the general population. We observed a significant increase in homocysteine in the 776GG vs. 776CC genotype, corroborating the influence of age as a determinant of homocysteine in relation to this polymorphism. When we analyzed vitamin B(12) and its relationship with the C776G polymorphism, we found no significant differences. Only 776CG/66AA or 776GG/66AG genotypes presented a significant increase in homocysteine when compared with other groups. In the multivariate analysis, transcobalamin II C776G (CC/CG vs. GG), methylenetetrahydrofolate reductase C677T (CC/CT vs. TT), folate, gender and age presented statistical significance in relation to the homocysteine. These can be considered independent risk factors for hyperhomocysteinemia in this children group. Our results, if confirmed in other populations, highlight the necessity for investigation of the transcobalamin II C776G polymorphism in the research for hyperhomocysteinemia risk factors.

Hyperhomocysteinemia is a risk factor for cardiovascular disease. C677T mutation at the MTHFR gene and deficiencies of folic acid and vitamin B-12 may account for elevation of total homocysteine (tHcy). Ninety Brazilian Parkatêjê Indians (90.0% of the population without admixture, aged > or = 20 years) were studied. Hyperhomocysteinemia was observed in 26.7% of the Indians. No case of vitamin B-12 deficiency was detected. Folic acid deficiency was found in 43.3% of the subjects. Rates of mutated allele 677T and TT genotype were 40.7% and 14.0%, respectively. Prevalence of hypertension, dyslipidemia, smoking, WHR > or = 0.9, BMI > or = 25 kg/m2 and chronic alcohol use were 4.4%, 44.4%, 25.6%, 72.2%, 67.8%, and 0.0%, respectively. All creatinine values were normal. Natural logarithmic (ln) tHcy showed no correlation with age, but was positively correlated with systolic (r = 0.22) and diastolic (r = 0.21) blood pressure and triglycerides (r = 0.39) and inversely correlated with folic acid (r = -0.40) adjusted for age and sex. Total homocysteine (tHcy) was higher among TT genotype (P < .001). The multiple linear regression model, containing variables for sex, folic acid, TT genotype, and triglycerides, explained 50.0% of the variation of the ln tHcy. In summary, high rates of cardiovascular risk factors were discovered. C667T mutation and folic acid deficiency can explain, at least in part, the observed hyperhomocysteinemia.

Hyperhomocysteinemia is a risk factor for thrombosis, and methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms, folate, and B12 levels could contribute to plasma homocysteine (Hcy) variation. Although well established in adults, few studies have been performed in childhood. In this study, we investigated association of polymorphisms C677T and A1298C in the MTHFR gene and A66G in the MTRR gene with Hcy levels in children. These polymorphisms, as well as Hcy, folate, and vitamin B12 levels were investigated in 220 normal children with ages ranging from 1 to 8 years. Plasma Hcy, folate, and vitamin B12 levels were normal in all children. None of the polymorphisms could be considered an independent risk factor for hyperhomocysteinemia during childhood. The median Hcy levels in 37 children (17%) doubly heterozygous for C677T and A1298C mutations in the MTHFR gene were not different from the other genotypes. However, the association of the different genotypes with Hcy, folate, and vitamin B12 levels demonstrated significant P-values. The folate levels demonstrated a statistically significant decrease (P = 0.0477) from the C677T mutation in the MTHFR gene (TT genotype) when compared to the other groups. Folate was the only independent risk factor for hyperhomocysteinemia. Thus, monitoring the concentrations of folate would be more helpful for evaluating hyperhomocysteinemia and for preventing cardiovascular disease., (Copyright 2004 Wiley-Liss, Inc.)