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Methylenetetrahydrofolate reductase (MTHFR): incidence of mutations C677T and A1298C in Brazilian population and its correlation with plasma homocysteine levels in spina bifida
Author(s) -
Perez Ana Beatriz Alvarez,
D'Almeida Vânia,
Vergani Naja,
de Oliveira Allan C.,
de Lima Fernanda Teresa,
Brui Decio
Publication year - 2002
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.10059
Subject(s) - methylenetetrahydrofolate reductase , homocysteine , spina bifida , allele , methionine , hyperhomocysteinemia , medicine , incidence (geometry) , genotype , white (mutation) , genetics , allele frequency , population , endocrinology , biology , gastroenterology , gene , physics , environmental health , optics , amino acid
Homocysteine (Hcy) is converted to cysteine or is remethylated to methionine by methylenetetrahydrofolate reductase (MTHFR). MTHFR plays a central role in the metabolism of folate. Two common polymorphisms in the MTHFR gene (C677T and A1298C) have been described and studies suggest that these polymorphisms are positively associated with the occurrence of spina bifida (SB). Among Brazilians, the incidence of 677T allele homozygosity is 4%. We compared Hcy levels with the genotypes obtained for the mutations C677T and A1298C in the gene MTHFR . Levels of plasma Hcy were higher in children with SB than in controls (average 7.95 vs. 5.55 (μmol/L); P < 0.001). There was no significant difference in the levels of Hcy for these childrens's mothers and controls (average 7.76 vs. 8.36 (μmol/L); P = 0.27). Eighty one (61.8%) of the affected children were white and 50 (38.2%) were non‐white. A similar ratio was observed in the mothers. In the control group, 51 children (40.5%) were white and 75 (59.5%) were non‐white, and 52 mothers (41.3%) were white and 74 (58.7%) were non‐white. There was no significant difference in the homozygous frequency for the mutated allele 677T among different racial groups. We obtained a prevalence of TT homozygosity of 10/131 (7.64%) in affected children and 13/126 (10.32%) in controls. With respect to the mutation A1298C, the homozygous prevalence for the wild allele was greater among non‐white individuals than in white individuals both in case and control groups. Hyperhomocysteinemia is a risk factor for SB. However, in our population, the increase in plasma levels of Hcy is not explained by the presence of the homozygous TT. It is possible that low folic acid intake combined with other genetic factors plays a more important role in the cause of this disease. © 2003 Wiley‐Liss, Inc.