TY - JOUR
T1 - The MTRR 66A>G polymorphism and maternal risk of birth of a child with Down syndrome in Caucasian women
T2 - A case-control study and a meta-analysis
AU - Coppedè, Fabio
AU - Bosco, Paolo
AU - Lorenzoni, Valentina
AU - Denaro, Maria
AU - Anello, Guido
AU - Antonucci, Ivana
AU - Barone, Concetta
AU - Stuppia, Liborio
AU - Romano, Corrado
AU - Migliore, Lucia
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Down syndrome
KW - Folate
KW - Homocysteine
KW - Meta-analysis
KW - Methionine synthase reductase
KW - MTRR 66A>G polymorphism
KW - Vitamin B12
UR - http://www.scopus.com/inward/record.url?scp=84906670769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906670769&partnerID=8YFLogxK
U2 - 10.1007/s11033-014-3462-5
DO - 10.1007/s11033-014-3462-5
M3 - Article
C2 - 24965145
AN - SCOPUS:84906670769
VL - 41
SP - 5571
EP - 5583
JO - Molecular Biology Reports
JF - Molecular Biology Reports
SN - 0301-4851
IS - 9
ER -