alexa Methylenetetrahydrofolate reductase polymorphisms C677T and A1298C as maternal risk factors for Down syndrome in Jordan.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Genetic Syndromes & Gene Therapy

Author(s): Sadiq MF, AlRefai EA, AlNasser A, Khassawneh M, AlBatayneh Q

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Abstract BACKGROUND: The activity of the methylenetetrahydrofolate reductase (MTHFR) enzyme is regulated by the two polymorphisms C677T and A1298C, which reduce enzyme activity and result in hypomethylation of chromosomes that increase the risk of nondisjunction. These polymorphisms are suggested to be risk factors for Down syndrome (DS) in some populations. AIM: The aim of this study was to test if C677T and A1298C polymorphisms are correlated to maternal risk of DS in Jordan. METHODS: The proportions of C677T and A1298C polymorphisms were examined in 53 case mothers who delivered DS children and 29 controls. The median age of case mothers was 35 years when delivering their affected children. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. RESULTS: The frequency of MTHFR C677T allele in all DS mothers was 3.2-fold higher than in the controls (odds ratio [OR] = 3.12, 95\% confidence interval [CI]: 1.303-7.677). Also, the proportion of 677T in the older case mothers was different from the controls, but was significantly higher in younger case mothers than in the controls (OR = 4.2, 95\% CI: 1.61-10.97, p = 0.003). The proportions of 677CT and 677TT genotypes in younger cases are, respectively, 10- and 9-fold higher than in the controls. The proportions of MTHFR A1298C are significantly different among all case groups and the controls (χ(2) = 4.27, p = 0.127), but there was a significant difference between young case mothers and both older case mothers group and the controls (OR = 1.25, 95\% CI: 0.405-3.85, p = 0.698). CONCLUSIONS: There is strong association between MTHFRC677T and maternal risk of DS in Jordanian mothers younger than 35 years old and the MTHFR1298C allele has a lesser but additive risk effect in MTHFR677T/1298C compound heterozygotes. This article was published in Genet Test Mol Biomarkers and referenced in Journal of Genetic Syndromes & Gene Therapy

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