How to Cite this Article: Zhu H, Yang W, Lu W, Etheredge AJ, Lammer EJ, Finnell RH, Carmichael SL, Shaw GM. 2012. Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects. Am J Med Genet Part A. 158A:1124–1134.
Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects†
Article first published online: 11 APR 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 5, pages 1124–1134, May 2012
How to Cite
Zhu, H., Yang, W., Lu, W., Etheredge, A. J., Lammer, E. J., Finnell, R. H., Carmichael, S. L. and Shaw, G. M. (2012), Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects. Am. J. Med. Genet., 158A: 1124–1134. doi: 10.1002/ajmg.a.35313
- Issue published online: 18 APR 2012
- Article first published online: 11 APR 2012
- Manuscript Accepted: 6 FEB 2012
- Manuscript Received: 11 JUL 2011
- NIH/NHLBI. Grant Number: R01 HL085859
- Centers for Disease Control and Prevention
- Center of Excellence Award. Grant Number: U50/CCU913241
- conotruncal defects;
- one carbon metabolism;
We evaluated 35 variants among four folate-mediated one-carbon metabolism pathway genes, MTHFD1, SHMT1, MTHFR, and DHFR as risk factors for conotruncal heart defects. Cases with a diagnosis of single gene disorders or chromosomal aneusomies were excluded. Controls were randomly selected from area hospitals in proportion to their contribution to the total population of live-born infants. Odds ratios (OR) and the 95% confidence intervals (CI) were computed for each genotype (homozygous variant or heterozygote, vs. homozygous wildtype) and for increase of each less common allele (log-additive model). Interactions between each variant and three folate intake variables (maternal multivitamin use, maternal dietary folate intake, and combined maternal folate intake) were also evaluated under the log-additive model. In general, we did not identify notable associations. The A allele of MTHFD1 rs11627387 was associated with a 1.7-fold increase in conotruncal defects risk in both Hispanic mothers (OR = 1.7, 95% CI = 1.1–2.5) and Hispanic infants (OR = 1.7, 95% CI = 1.2–2.3). The T allele of MTHFR rs1801133 was associated with a 2.8-fold increase of risk among Hispanic women whose dietary folate intake was ≤25th centile. The C allele of MTHFR rs1801131 was associated with a two-fold increase of risk (OR = 2.0, 95% CI = 1.0–3.9) only among those whose dietary folate intake was >25th centile. Our study suggested that MTHFD1 rs11627387 may be associated with risk of conotruncal defects through both maternal and offspring genotype effect among the Hispanics. Maternal functional variants in MTHFR gene may interact with dietary folate intake and modify the conotruncal defects risk in the offspring. © 2012 Wiley Periodicals, Inc.