Maternal gene polymorphisms involved in folate metabolism as risk factors for Down syndrome offspring in Southern Brazil.
This study aimed to investigate the role of maternal polymorphisms, as well as their risk genotypes combinations of MTR A2756G, MTRR A66G, CBS 844ins68, and RFC A80G, involved in folate/homocysteine metabolism, as possible risk factors for Down syndrome (DS) in Southern Brazil. A case-control study was conducted with 239~mothers of DS children and 197~control mothers. The investigation of polymorphisms was performed by PCR and PCR-RFLP. The distribution of genotypic variants was similar in both groups when they were analyzed separately. An investigation of combined risk genotypes showed that the risk of having a DS child for one, two or three risk genotypes was 6.23, 6.96 and 5.84 (95%CI 1.48-26.26; 1.69-28.66; 1.37-24.86), respectively. The combined MTRR 66G and MTHFR 677T alleles were significantly more common among mothers of children with DS than among control mothers (OR 1.55; IC 95% 1.03-2.35). The results show that individual polymorphisms studied in this work are not associated with DS; however, the effects of the combined risk genotypes among MTR, MTRR, CBS and RFC genes are considered maternal risk factors for DS offspring in our population.
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
Ana Paula Carneiro
AP
Brandalize
Eliane
E
Bandinelli
Pollyanna Almeida
PA
Dos Santos
Lavínia
L
Schüler-Faccini
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D003541:Cystathionine beta-Synthase / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008423:Maternal Age; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D012307:Risk Factors
D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase