High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects

Mol Genet Metab. 1999 Dec;68(4):461-7. doi: 10.1006/mgme.1999.2939.

Abstract

Neural tube defects (NTD) are highly prevalent in the Mexican population. According to data from the Registry and Epidemiological Surveillance of External Congenital Malformations (RYVEMCE), at least 1 in 250 conceptions that reach 20 weeks of pregnancy or more has a NTD. This number is three to four times higher than that observed in other related ethnic groups. A common novel mutation (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene is considered an associated risk factor for NTD and other malformations. Studies in different populations agree that the prevalence of the homozygote for the mutated allele is higher in cases of NTD than in controls. In a meta-analysis recently published, the mean prevalence of the homozygote for the mutation was 9.2% for different groups of European controls and 16.4% in NTD cases from the same populations. This prompted us to investigate the frequency of the normal (C) and the mutant (T) alleles and the prevalence of the expected (CC, CT and TT) genotypes in 250 healthy Mexican women from different parts of the country. The proportion of CC (17.6%), CT (47.6%), and TT (34. 8%) genotypes found, and the gene frequencies of 0.414 and 0.586% for the C and T alleles, respectively, confirmed the very high prevalence of the mutant allele and the TT genotype in the sample studied. Comparisons with studies done in Holland, Ireland, the United States, Japan, and other ethnic groups showed highly significant differences, with an average OR of 5.8 (95% Cl 3.4-10.3) for a Mexican being homozygous for the mutation. These findings may explain an important part of the high prevalence of NTD observed in our population.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • DNA Mutational Analysis
  • Female
  • Gene Frequency / genetics*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Mexico / epidemiology
  • Mutation, Missense / genetics*
  • Neural Tube Defects / epidemiology*
  • Neural Tube Defects / ethnology
  • Neural Tube Defects / genetics
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Pregnancy
  • Prevalence

Substances

  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)