Association between polymorphisms in maternal genes of folate metabolism and down syndrome

Abstract

Down syndrome is a complex genetic and metabolic disorder attribute to the presence of three copies of chromosome 21. It is the leading genetic cause of mental retardation and is estimated to occur 1/600 - 1,000 live births. The origin of extra chromosome is due to abnormal chromosomal segregation during meiosis (non disjunction). Except for advanced maternal age at conception, maternal risk factors for meiotic non disjunction are unknown. Previous studies found an association between polymorphisms in maternal genes of folate metabolism and Down syndrome. However, it is still controversial. Some recent studies showed contradictory findings. We performed an association study between MTHFR 677C- >T, MTHFR 1298A->C, MTRR 66A->G and MTR 2756A->G polymorphisms and the risks of Thai women having children with Down syndrome. We analyzed 109 case mothers and 186 control mothers for the polymorphisms by PCR amplification followed by restriction enzyme digestion analysis. There were no significant difference between groups in term of mean age at conception (case = 33.9±.5.81, control = 32.4± 5.12; x²=0.034, p= 0.85). Our data show that MTHFR 677T and MTRR 66G allele frequencies in Thai are 0.15 and 0.28, respectively. These are relatively low compared with those in other population. The MTHFR1298C and MTR2756G allele frequencies are 0.28 and 0.15, respectively. These frequencies are comparable to those in other populations. The results found no difference in the allele and genotype frequencies of MTHFR 677C->T, MTHFR 1298A->C, MTRR 66A->G and MTR 2756A->G between Thai mothers of Down syndrome and controls. Moreover, we found no difference in the haplotype frequencies of MTHFR in case compared with control group. In conclusion, our results do not support the presence of an increased risk of Down syndrome in mothers carrying of the MTHFR, MTRR and MTR polymorphisms in Thai population.