Affiliations: Department of Genetics, Institute of Child Health,
'Aghia Sophia' Children's Hospital, Athens, Greece | Department of Medical Genetics, John F. Kennedy
Institute, Glostrup, Denmark | Department of Pediatrics, Athens University Medical
School, Athens, Greece
Note: [] Corresponding author: Dr. Michael B. Petersen, Department of
Genetics, Institute of Child Health, 'Aghia Sophia' Children's Hospital, Thivon
& Levadias, GR-115 27, Athens, Greece. Tel.: +30 213 2037330; Fax: +30 210
7700111; E-mail: mpetersen@ich.gr
Abstract: Chromosomal aneuploidy consists the leading cause of fetal death in
our species. Around 50% of spontaneous abortions until 15 weeks of gestational
age are chromosomally aneuploid, with trisomies accounting for 50% of the
abnormal abortions. Trisomy 21 is the most common chromosome abnormality in
liveborns and is usually the result of nondisjunction of chromosome 21 in
meiosis in either oogenesis or spermatogenesis. To investigate the relationship
between folate metabolism and Down syndrome (DS) in a Danish population, we
analyzed the common 677C>T genetic polymorphism in the
methylenetetrahydrofolate reductase (MTHFR) gene. Our cohort consisted of 181
mothers of children with DS versus 1,084 healthy controls. Polymerase chain
reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to
examine the MTHFR 677C>T polymorphism. No significant association between
the polymorphism and the risk for DS was found. We conclude that the common
MTHFR 677C>T polymorphism is not likely to be a maternal risk factor for DS
in our cohort and that the difference to previous studies can probably be
explained by small sample size or geographic variation in gene polymorphisms
involving gene-nutritional or gene-gene or gene-nutritional-environmental
factors.
Keywords: Down syndrome, nondisjunction, MTHFR, polymorphism, risk factor
