Background: The 5,10-methylenetetrahydrofolate reductase ( MTHFR )
polymorphisms and low folate levels are associated with inhibition of
DNA methyltransferase and consequently DNA hypomethylation. The
expanding spectrum of common conditions linked with MTHFR
polymorphisms includes certain adverse birth outcome, pregnancy
complications, cancers, adult cardiovascular diseases and psychiatric
disorders, with several of these associations remaining still
controversial. Trisomy 21 or Down syndrome (DS) is the most common
genetic cause of mental retardation. It stems predominantly from the
failure of chromosome 21 to segregate normally during meiosis. Despite
substantial research, the molecular mechanisms underlying
non-disjunction leading to trisomy 21 are poorly understood. Materials
and Methods: Two common variants C677T and A1298C of the MTHFR gene
were screened in 36 parents with DS children and 60 healthy couples
from Tamil Nadu and Karnataka. The MTHFR genotypes were studied by
RFLP analysis of PCR-amplified products and confirmed by sequencing.
Results: The CT genotype was seen in three each (8.3%) of case mothers
and fathers. One case father showed TT genotype. All the control
individuals exhibited the wild type CC genotype. A similar frequency
for the uncommon allele C of the second polymorphism was recorded in
case mothers (0.35) and fathers (0.37) in comparison with the control
mothers (0.39) and fathers (0.37). Conclusion: This first report on
MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south
Indian population revealed that MTHFR 677CT polymorphism was
associated with a risk for Down syndrome