title: Association of methylenetetrahydrofolate reductase gene 677C > T polymorphism and Down syndrome.
abstract: The association between Down syndrome (DS) and maternal polymorphisms in genes encoding folic acid metabolizing enzymes remains a controversial issue. A meta-analysis was performed to evaluate the association of maternal MTHFR 677C > T polymorphism and the risk of having a child with DS. Case-control studies were screened from major literature databases. Twenty articles from 13 countries worldwide, with a total of 2,101 DS and 2,702 control mothers, attended the inclusion criteria. We found a 50 % increase for the association of maternal homozygous TT genotype and DS in both fixed (OR = 1.51; 95 % CI 1.22-1.87) and random effects models (OR 1.54; 95 % 1.15-2.05). Similarly, a significant pooled OR was found for the heterozygote CT, with an OR 1.26; 95 % CI 1.10-1.43 (fixed effects model) and OR 1.28; 95 % 1.08-1.51 (random effects model). As ultra-violet B solar radiation highly depends on latitude, and can promote, in less pigmented skin, intravascular folate photolysis, we stratified the analysis by latitude region, defining as Tropical (between 23.5(°) S and 23.5(°) N), Sub-Tropical (between 23.5(°) and 40(°) N and S), and Northern (≥ 40(o) N). Significant association was only found for Sub-Tropical area, both using fixed and random effect models. In conclusion, MTHFR 677C > T polymorphism is a moderate risk factor for DS for some populations, and populations located in Sub-Tropical region seem to be at greater risk. Latitude, ethnicity, skin pigmentation, and red blood cell folate are important variables to be considered in future studies.
authors.affiliation: Departamento de Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcelo Aguiar
authors.initials: MA
authors.lastname: Costa-Lima
authors.forename: Márcia Rodrigues
authors.initials: MR
authors.lastname: Amorim
authors.forename: Iêda Maria
authors.initials: IM
authors.lastname: Orioli
mesh_terms: D000483:Alleles; D002648:Child; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009035:Mothers; D016017:Odds Ratio; D011110:Polymorphism, Genetic
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)