BACKGROUND: Mechanisms underlying meiotic nondisjunction are poorly understood. Attempts to elucidate the causes of Down syndrome (DS) have analyzed the relationship between polymorphism in folate metabolism and DS. AIM: The role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A and betaine-homocysteine methyltransferase (BHMT) G742A polymorphisms in DS risk was investigated. METHODS: Blood samples were collected from a total of 86 DS mothers and from 161 control mothers. The investigation of the MTHFD1 G1958A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and by real-time PCR for the BHMT G742A polymorphism. RESULTS: The median maternal age of case mothers (30.40; 12.9-46.3 years) was significantly higher (p<0.0005) than in the control group (26.60; 15.4-57.9 years). The frequency of BHMT variant genotypes was significantly lower in DS mothers compared with controls (p=0.047). A significant decreased risk for BHMT 742 AA genotype (odds ratio [OR]=0.30; 95% confidence interval [CI]: 0.10-0.93; p=0.037) was observed. Moreover, when the dominant model was applied (BHMT 742GA or 7428AA versus 742GG), there was also a significant decrease in DS risk (OR=0.58; 95% CI: 0.37-0.98; p=0.042). MTHFD1 G1958A genotype frequencies were not significantly altered in DS mothers (p=0.206). CONCLUSIONS: Our study suggests that the polymorphism BHMT G742A may modulate the DS risk in Brazilian mothers.
BACKGROUND: Mechanisms underlying meiotic nondisjunction are poorly understood. Attempts to elucidate the causes of Down syndrome (DS) have analyzed the relationship between polymorphism in folate metabolism and DS. AIM: The role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A and betaine-homocysteine methyltransferase (BHMT) G742A polymorphisms in DS risk was investigated. METHODS: Blood samples were collected from a total of 86 DS mothers and from 161 control mothers. The investigation of the MTHFD1G1958A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and by real-time PCR for the BHMTG742A polymorphism. RESULTS: The median maternal age of case mothers (30.40; 12.9-46.3 years) was significantly higher (p<0.0005) than in the control group (26.60; 15.4-57.9 years). The frequency of BHMT variant genotypes was significantly lower in DS mothers compared with controls (p=0.047). A significant decreased risk for BHMT 742 AA genotype (odds ratio [OR]=0.30; 95% confidence interval [CI]: 0.10-0.93; p=0.037) was observed. Moreover, when the dominant model was applied (BHMT 742GA or 7428AA versus 742GG), there was also a significant decrease in DS risk (OR=0.58; 95% CI: 0.37-0.98; p=0.042). MTHFD1G1958A genotype frequencies were not significantly altered in DS mothers (p=0.206). CONCLUSIONS: Our study suggests that the polymorphism BHMTG742A may modulate the DS risk in Brazilian mothers.
Authors: Rebecca A Jackson; Mai Linh Nguyen; Angela N Barrett; Yuan Yee Tan; Mahesh A Choolani; Ee Sin Chen Journal: Cell Mol Life Sci Date: 2016-05-31 Impact factor: 9.261
Authors: Márcia R Amorim; Cláudia M Moura; Aline D Gomes; Hazel N Barboza; Roberta B Lopes; Márcia G Ribeiro; Marcelo A Costa Lima Journal: Mol Biol Rep Date: 2013-05-05 Impact factor: 2.316