Maternal Folate Gene Polymorphisms as Risk Factors for Down Syndrome in Egypt
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- Category: Vol. 82, December 2014
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Maternal Folate Gene Polymorphisms as Risk Factors for Down Syndrome in Egypt, HANAN H. AFIFI, KHALDA S. AMR, ANGIE M.S. TOSSON, MANAL M. THOMAS and MAHA M. EID
Abstract
Many contradictory studies have been published on the genetic polymorphisms in genes involved in folate metabolism and the risk of having a Down syndrome (DS) offspring. This case-control study aimed to investigate the maternal risk for DS offspring in Egypt, by analysis of independent and com-bined genotypes of methylenetetrahydrofaolate reductase (MTHFR C677T and A1298C) and methionine synthase (MTR A2756G). Seventy three young mothers and 43 old mothers, of proven non-disjunction DS offspring and 100 age-matched control mothers with normal children were included. PCR-RFLP analysis of the three polymorphisms was performed and Allele/genotype frequencies were determined. Results revealed that genotyping of the polymorphisms studied either individually or combined and haplotype risk alleles exhibited a similar frequency in both groups of old and young mothers of DS. The combined genotypes of MTHFR 677CC with MTHFR 1298CC+AC, MTHFR 677TT+CT with MTR 2756AA, MTHFR 1298CC+AC with MTR 2756 AA were more significant among mothers of DS (p=0.001) with the following increased odd ratios of 17.6, 27.05, and 11.58, respectively. The combined genotypes of three polymorphisms MTHFR 677CC with MTHFR 1298CC+AC and MTR 2756AA, and MTHFR 677TT+CT with MTHFR 1298CC+AC and MTR 2756AA were more significant among mothers of DS (p=0.001) with the following increased odd ratios 17.06 and 31.29 respectively. Haplotype risk alleles of MTHFR 677T & 1298C and MTR 2756A was associated with cases 20.89 fold increased odd ratio. The same parameters showed high odd ratios among young mothers of DS and controls; and old mothers of DS and controls. In conclusion, combined genotypes and allele haplotypes among MTHFR 677, MTHFR 1298 and MTR 2756 polymorphisms are considered maternal risk factors for DS offspring in our population.