Relationships between gene polymorphisms of folate-related proteins and vitamins and metabolites in pregnant women and neonates.
BACKGROUND
The methylenetetrahydrofolate reductase (MTHFR), glutamate carboxypeptidase II (GCPII) and reduced folate carrier (RFC1) gene polymorphisms were associated with folate status. We investigated the effects of these polymorphisms on serum folate (SF) and folate-related metabolites in mothers and their neonates.


METHODS
Cobalamin (Cbl), SF, total homocysteine (tHcy), methylmalonic acid (MMA), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured in 275 healthy women and their neonates. MTHFR C677T, GCPII C1561T and RFC1 A80G polymorphisms were determined by PCR-RFLP.


RESULTS
Maternal tHcy was affected individually by MTHFR C677T and GCPII C1561T polymorphisms and by combined genotypes MTHFR 677TT/GCPII 1561CC and MTHFR 677TT/RFC1 80AG. The MTHFR and RFC1 polymorphisms were not associated with variations in vitamins or SAM, SAH and MMA in neonates. Neonatal tHcy was predicted directly by maternal tHcy and inversely by maternal SF, neonatal Cbl and neonatal RFC1 80G allele (AG+GG genotypes). Maternal MMA and SAM/SAH were predicted by creatinine and Cbl, respectively. Neonatal MMA was predicted by maternal MMA and GCPII 1561T allele (CT+TT genotypes) and by neonatal Cbl.


CONCLUSIONS
Maternal tHcy was affected by MTHFR C677T, RFC1 A80G and GCPII C1561T polymorphisms. Maternal GCPII C1561T variant was associated with neonatal MMA. Neonatal RFC1 A80G polymorphism influenced tHcy in neonates.
Lopreato
Fernanda R
FR
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, Brazil.
Stabler
Sally P
SP
Carvalho
Felipe R
FR
Hirata
Rosario D C
RD
Hirata
Mario H
MH
Robi
Débora L
DL
Sampaio-Neto
Luiz F
LF
Allen
Robert H
RH
Guerra-Shinohara
Elvira M
EM
D000328:Adult; D001938:Brazil / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D047108:Embryonic Development / Q000187:drug effects; D005006:Ethnicity; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D043425:Glutamate Carboxypeptidase II / Q000235:genetics*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D008764:Methylmalonic Acid / Q000097:blood; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy / Q000378:metabolism*; D058978:Reduced Folate Carrier Protein / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood; D012959:Socioeconomic Factors; D014805:Vitamin B 12 / Q000097:blood; D014803:Vitamin B Complex / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D006710:Homocysteine; D014803:Vitamin B Complex; D012436:S-Adenosylmethionine; D008764:Methylmalonic Acid; D004247:DNA; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D043425:Glutamate Carboxypeptidase II; D014805:Vitamin B 12