Maternal polymorphisms 677C‐T and 1298A‐C of MTHFR, and 66A‐G MTRR genes: Is there any relationship between polymorphisms of the folate pathway, maternal homocysteine levels, and the risk for having a child with Down syndrome?

摘要: This study was aimed at analyzing the effect of mutations in three non-synonymous SNP genes (677C > T and 1298A C methylenetetrahydrofolate reductase (MTHFR) gene, 66A G MTRR gene) on total plasmatic homocysteine (Hcy), 91 mothers Down syndrome (DS) infants 90 control mothers. The comparison both groups is a new way to determine if those their interactions increase risk for DS. Material came from case-control network Spanish Collaborative Study Congenital Malformations (ECEMC). Using general lineal model backwards step, we performed analyses including different mutations, maternal age, fact that each mother had DS or infant, all possible these variables, models, being Hcy continuous dependent variable. In another model, folic acid intake during third trimester pregnancy added. results models were essentially same: levels variability differs case ones, presence MTHFR1298A polymorphism also affects significantly variance, as it does statistical interaction between MTRR66A mother. this sense, polymorphisms may totally modify individual effects, some effects are children controls' For instance, only two MTRR66 (GGAA) reference level 4.66 units, genotype with MTHFR1298 gene (AACC) increases 12.74 units. However, four (GGCC) interacts giving statistically significant decrease 6.00 units On contrary, infants, sole one decreases (-2.31 GGAA genotype, -3.43 AACC genotype), while 9.53 Taking into consideration one-carbon metabolism cystathionine beta-synthase (CBS) catalyzes an irreversible way, CBS located chromosome 21, fetuses have functional folate deficiency due overexpression CBS. fact, well others influencing (such nutrients lifestyle), together fetal suggest relationship could be through survival up birth. Three mechanisms considered by evaluating light present knowledge cytology molecular biology.