OA Epidemiology

Interactions between maternal diabetes mellitus, MTHFR 677C>T and periconceptional folate supplementation in the risk of congenital anorectal malformations

Proceedings of the 2013 annual meeting of the Netherlands Epidemiology Society

Volume 1 Issue S1 Abstract 58

 

C.H.W. Wijers, Radboud University Nijmegen Medical Centre, Nijmegen
I. de Blaauw, Sophia Children’s Hospital-Erasmus MC, Rotterdam
L.F.M. van der Zanden, Radboud University Nijmegen Medical Centre, Nijmegen
C.L.M Marcelis, Radboud University Nijmegen Medical Centre, Nijmegen
A.S. Brooks, Erasmus MC, Rotterdam
P.M.A. Broens, University Medical Center Groningen, Groningen
R.M. Wijnen, Sophia Children’s Hospital-Erasmus MC, Rotterdam
R.M Hofstra, Erasmus MC, Rotterdam
H.G. Brunner, Radboud University Nijmegen Medical Centre, Nijmegen
N. Roeleveld, Radboud University Nijmegen Medical Centre, Nijmegen
I.A.L.M. van Rooij, Radboud University Nijmegen Medical Centre, Nijmegen

Background
Based on suggestions from the literature, we aimed to investigate interactions between maternal diabetes mellitus, the MTHFR (methylenetetrahydrofolate reductase) 677C>T polymorphism, and periconceptional folate supplementation and the risk of congenital anorectal malformations (ARM).

Methods
We conducted a case-control study among 522 nonsyndromic ARM cases and 2,139 population-based controls within the AGORA biobank.  Maternal questionnaires were used to obtain information on preexisting diabetes and use of supplements containing folic acid during 4 weeks before through 10 weeks after conception. DNA samples of mothers and children were genotyped for the MTHFR 677C>T polymorphism in a subset of 367 cases and 697 controls. Odds ratios for independent and joint effects were estimated. The study population will be extended with 155 German cases and 646 German controls shortly.

Results
No independent association was found between ARM and a lack of peri-concep¬tional folic acid use (OR=0.9; 95%CI:0.7-1.2), whereas preexisting diabetes seemed to increase the risk of ARM (OR=2.8; 95%CI:0.9-8.11). A joint association between ARM and diabetes plus a lack of folic acid use was not observed. Neither were child and maternal MTHFR 677CT/TT genotypes found to increase the risk. However, both child and maternal MTHFR 677CT/TT genotypes in combination with a lack of periconceptional folic acid use seemed to be associated with a small increased risk of ARM (OR=1.3; 95%CI:0.9-2.0 and OR=1.2; 95%CI:0.8-1.9, respectively). The relative excess risks suggest interactions on an additive scale (RERIs > 0).

Conclusions
These preliminary results point towards a role of gene-environment interactions in the etiology of ARM.

Published: 06 Jun, 2013

 
Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)