Details

Autor(en) / Beteiligte

• Bufalino, Andreia
• Ribeiro Paranaíba, Lívia Máris
• Nascimento de Aquino, Sibele
• Martelli-Júnior, Hercílio
• Oliveira Swerts, Mario Sergio
• Coletta, Ricardo D.

Titel

Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population

Ist Teil von

• Birth defects research. A Clinical and molecular teratology, 2010-11, Vol.88 (11), p.980-986

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGROUND Polymorphisms in genes that are involved in folic acid metabolism may be important maternal risk factors for the birth of a child with nonsyndromic cleft lip and/or palate (NSCL/P). The aim of this study was to determine the involvement of polymorphic variants in four genes (MTHFR, MTHFD1, MTR, and SLC19A1) that encode proteins related to folic acid metabolism in the women with susceptibility for having a child with NSCL/P. METHODS DNA samples from 106 mothers of children with NSCL/P (case group) and from 184 mothers of healthy children (control group) were genotyped by polymerase chain reaction associated with restriction fragment length polymorphism (PCR‐RFLP). RESULTS One of 29 polymorphisms was associated with significantly increased maternal risk for NSCL/P. Mothers exhibiting the A variant allele (GA genotype) of the MTHFR rs2274976 polymorphism demonstrated a ∼6 times increased risk for having a child with NSCL/P compared to G allele carriers (OR, 5.76; 95% CI, 3.32–9.99, p = 0.000001). Among mothers who did not use vitamins, the OR of NSCL/P was increased to 8.34 (95% CI, 3.75–18.55, p = 0.000001) in the presence of the GA genotype of the MTHFR rs2274976 polymorphism compared to those with the GG genotype. Gene‐gene interaction analysis showed that the combination of MTHFR rs2274976, MTHFD1 rs2236225, and SLC19A1 rs1051266 was the best model for prediction of maternal risk for NSCL/P. CONCLUSION The findings of the present study suggested that genetic variants of folic acid metabolic genes may modulate maternal susceptibility for having an offspring with NSCL/P. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.