title: [Analysis of the frequencies of genotype combinations of 4 polymorphisms of genes acting on the folate cycle in the Spanish population].
abstract: OBJECTIVE
  Studies on different populations have shown a great variability of the frequencies of different polymorphisms in genes acting in the folate cycle. The present study was aimed to analyze the frequency in the Spanish population of each genotype combination of four polymorphisms, one of them -1561C-T of the glutamate carboxypeptidase II (GCPII) gene- being the first time that is studied in Spain. The study included a meta-analysis of the published data.
  
  
  METHODS
  Using the Spanish Collaborative Study of Congenital Malformations (ECEMC) Network, blood samples of 190 mother-child couples with newborns without any congenital defect, were obtained from 15 Spanish autonomous regions. The study polymorphisms were the 677C-T and 1298A-C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR), the 66A-G of the methionine synthase reductase (MTRR), and the 1561C-T polymorphism of the GCPII gene. To estimate the range for the population frequencies, 99% confidence intervals were calculated.
  
  
  RESULTS
  The frequencies observed in our country were significantly different from others, being similar to those obtained in countries of the Mediterranean European area. The 1561C-T polymorphism of the GCPII gene has a frequency in Spain of 5.11%, which is also similar to the values observed in France (5%) and in Italy (6%). On the other hand, the frequency of the genotypes CTCC, TTAC is quite few, while the genotype TTCC was not observed in any mother or infants. A meta-analysis was performed for a big sample (23,612 individuals) and the results showed that with a 99% of probability the values for the genotype combinations CTCC, TTAC, and TTCC were within 0.10-0.24; 0.20-0.36; and 0.003-0.05, respectively.
  
  
  CONCLUSIONS
  Our results are important to further analyze the relationship with some health problems and individual susceptibilities. Indeed, considering the published observations of the structure and function of the MTHFR enzyme, it is understandable that those genotype combinations that are quite little frequent, may be related to the embryo-fetal viability, and to the life style of each population.
authors.affiliation: Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III (ISCIII), Ministerio de Sanidad y Consumo, Madrid, España. mlmartinez.frias@isciii.es
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Frías
authors.forename: Eva
authors.initials: E
authors.lastname: Bermejo
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez
authors.forename: Lourdes R
authors.initials: LR
authors.lastname: Desviat
authors.forename: Margarita
authors.initials: M
authors.lastname: Castro
authors.forename: Fátima
authors.initials: F
authors.lastname: Leal
authors.forename: Elena
authors.initials: E
authors.lastname: Mansilla
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Fernández
authors.forename: Elvira
authors.initials: E
authors.lastname: Rodríguez-Pinilla
authors.forename: Laura
authors.initials: L
authors.lastname: Rodríguez
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ugarte
mesh_terms: D000954:Antigens, Surface / Q000235:genetics*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D043425:Glutamate Carboxypeptidase II / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009035:Mothers
chemical_list: D000954:Antigens, Surface; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II