title: The MTRR 66A>G polymorphism and maternal risk of birth of a child with Down syndrome in Caucasian women: a case-control study and a meta-analysis.
abstract: We performed a large case-control study and a meta-analysis of the literature to address the role of the methionine synthase reductase (MTRR) c.66A>G polymorphism as a maternal risk factor for the birth of a child with Down Syndrome (DS) among Caucasian women. A total of 253 mothers of a DS child (MDS) and 298 control mothers of Italian origin were included in the case-control study. The meta-analysis of previous and present data involved a total of seven studies performed in Caucasian populations (971 MDS and 1,387 control mothers). Results from the meta-analysis indicated overall a positive significant association between MTRR c.66A>G genotype [OR 1.36 (95 % CI 1.10-1.68), dominant model] and allele frequencies [OR 1.26 (95 % CI 1.04-1.51), allele contrast model] and maternal risk of birth of a child with DS. A sensitivity analysis revealed some interesting differences between Europeans, Caucasians of European descent, and inhabitants of Mediterranean regions, suggesting the possibility of population-specific modifying factors. The case-control study revealed association of the polymorphism with increased folate levels, and a possible interaction with the methionine synthase (MTR) c.2756A>G one, that resulted in a borderline significant maternal risk of birth of a child with DS for the double heterozygous MTR 2756AG/MTRR 66AG genotype [OR 1.79 (95 % CI 1.00-3.18)]. Overall, present data suggest that the MTRR c.66A>G polymorphism represents a risk factor for the birth of a child with DS among white Caucasian women. However, the combined presence of other genetic factors and interactions with geographic and environmental ones, can modify the effect of the single polymorphism alone, leading to population specific effect sizes.
authors: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy, f.coppede@geog.unipi.it.
authors: Fabio
authors: F
authors: Coppedè
authors: Paolo
authors: P
authors: Bosco
authors: Valentina
authors: V
authors: Lorenzoni
authors: Maria
authors: M
authors: Denaro
authors: Guido
authors: G
authors: Anello
authors: Ivana
authors: I
authors: Antonucci
authors: Concetta
authors: C
authors: Barone
authors: Liborio
authors: L
authors: Stuppia
authors: Corrado
authors: C
authors: Romano
authors: Lucia
authors: L
authors: Migliore
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009035:Mothers; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood; D044465:White People / Q000235:genetics*
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D014805:Vitamin B 12