Polymorphisms in the methylenetetrahydrofolate reductase and methionine synthase reductase genes and homocysteine levels in Brazilian children.
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.
Aléssio
Ana Claudia M
AC
Hematology-Hemotherapy Center, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Annichino-Bizzacchi
Joyce M
JM
Bydlowski
Sergio P
SP
Eberlin
Marcos N
MN
Vellasco
Adriana P
AP
Höehr
Nelci Fenalti
NF
D001938:Brazil; D002648:Child; D002675:Child, Preschool; D005287:Ferredoxin-NADP Reductase / Q000235:genetics* / Q000378:metabolism; D005492:Folic Acid / Q000097:blood / Q000378:metabolism; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis* / Q000235:genetics*; D007223:Infant; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood / Q000378:metabolism
D006710:Homocysteine; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12