Polymorphisms in the methylenetetrahydrofolate reductase and methionine synthase reductase genes and homocysteine levels in Brazilian children

Abstract

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.

Folate, vitamin B12 and total homocysteine levels in neonates from Brazil

“…Although we have not determined the normal levels of folate and vitamin B12 in cord blood samples from subjects of the general population, the folate and vitamin B12 values showed here are in agreement with reports in other Brazilian populations (Guerra-Shinohara et al, 2002; Alessio et al, 2004).…”

“…Here we showed that tHcy levels are higher among newborns of mother from low socioeconomic status when compared to those born from healthier mothers; in addition, there was a negative correlation between tHcy and folate. The same correlation was found in recent report among normal Brazilian children (from 1 to 8 years old) from Southeast Brazil (Alessio et al, 2004). The transient hypermocyteinaemia and mild hypertriglyceridemia have been associated to an inflammatory activation of the endothelium (Mansoor et al, 2004).…”

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Acute Lymphoblastic Leukemia Risk: A Meta-analysis

“…In fact, we also previously showed a lack of association between the A1298C genotypes and serum folate, serum cobalamin, or total homocysteine specifically in a mild folate-deficient Brazilian population (9). Indeed, despite some inverse positive associations (33), most current available data suggest no evidence for a major role of this variant in folate status (34) or homocysteine levels (9,35) in populations usually characterized by mild folate deficiency. Given the presence of heterogeneity among study results and the effect in an opposite direction for the A1298C variant found in some reports (22,32), we suggest that no additional studies are needed on this postulated association, at least for populations with adequate folate intake (30,31).…”

The MTR A2756G polymorphism is associated with an increase of plasma homocysteine concentration in Brazilian individuals with Down syndrome

“…However, Fillon-Emery et al (11) found no difference in Hcy concentrations according to the MTHFR C677T genotype in adults with trisomy 21, but observed an increase in Hcy concentrations in the presence of genotypes MTHFR 1298 AA and AC as compared to the mutated homozygote (CC) in a group of patients taking folic acid supplements. Studies on other populations have not detected any significant differences in Hcy concentrations between A1298C genotypes (28,29). However, elevated Hcy concentrations have been reported for the double heterozygote 677CT/1298AC (30).…”