Abstract: Down Syndrome (DS) is the most common genetic cause of intellectual disability. The incidence is increased in advanced maternal age of more than 35 years and mostly caused by meiotic non disjunction. MTHFR gene polymorphism has been identified as a genetic contributor to human meiotic non disjunction. This research aimed to analyze MTHFR C677T and A1298C polymorphisms as a risk factor for mothers to have children with classical DS. This study was an observational analytical study with case-control design. Blood samples were obtained from 30 mothers with cytogenetically confirmed children with classical DS (47, XX, +21 or 47, XY,+21) and 30 mothers of children without DS as controls. The DNA was extracted using salting out method, followed by PCR-RFLP analysis for MTHFR C677T and A1298C gene polymorphisms. The genotype frequency for MTHFR C677T was 56.7% homozygous CC (wild type) and 43.4% heterozygous CT in the cases and 63.4% homozygous CC (wild type), 33.3% heterozygous CT (heterozygote) and 3.3% homozygous TT (mutant type) in the controls. The genotype frequency for MTHFR A1298C was 50% homozygous AA (wild type), 43.3% heterozygous AC and 6.7% homozygous CC (mutant type) in the cases and 76.7% homozygous AA (wild type), 20% heterozygous AC and 3.3% homozygous CC (mutant type) in the controls. MTHFR C677T was inconclusive as risk factor for having children with DS (p = 0.598 or = 1.321, CI 95% = 0.46-3.72) whereas MTHFR A1289C was a risk factor for having children with DS (p = 0.014 or = 4.62, CI 95% = 1.36-15.65) in 73.3% young maternal age (<35 years). An MTHFR 1298C allele is a risk factor for mothers to have children with DS with a risk of 4.62 times higher compared with mother who has 1298A allele.
Tiar M. Pratamawati, Tri Indah Winarni, Hardian and Sultana M.H. Faradz, 2018. Maternal MTHFR A1298C not C677T Polymorphism as the Risk Factor in Children with Down Syndrome. Research Journal of Medical Sciences, 12: 84-89.