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Association between selected folate pathway polymorphisms and nonsyndromic limb reduction defects: a case–parental analysis
Author(s) -
Cleves Mario A.,
Hobbs Charlotte A.,
Zhao Weizhi,
Krakowiak Patrycja A.,
MacLeod Stewart L.
Publication year - 2011
Publication title -
paediatric and perinatal epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.667
H-Index - 88
eISSN - 1365-3016
pISSN - 0269-5022
DOI - 10.1111/j.1365-3016.2010.01160.x
Subject(s) - methylenetetrahydrofolate reductase , multivitamin , medicine , single nucleotide polymorphism , offspring , pregnancy , poisson regression , snp , relative risk , genetic association , genetics , allele , confidence interval , gene , genotype , biology , population , vitamin , environmental health
Summary Cleves MA, Hobbs CA, Zhao W, Krakowiak PA, MacLeod SL, the National Birth Defects Prevention Study. Association between selected folate pathway polymorphisms and nonsyndromic limb reduction defects: a case–parental analysis. Paediatric and Perinatal Epidemiology 2011. Inadequate folate status resulting from either genetic variation or nutritional deficiencies has been associated with an increased risk of congenital malformations including orofacial clefting, limb, cardiac and neural tube defects. Few epidemiological studies have examined the association between limb reduction defects (LRDs) and folate‐related genetic polymorphisms other than MTHFR 677C→T. We conducted a case–parental analysis of 148 families who participated in the National Birth Defects Prevention Study to examine the association between nonsyndromic transverse and longitudinal LRDs with five single nucleotide polymorphisms (SNPs) in genes encoding enzymes in folate and methionine pathways. Log‐linear Poisson regression, adapted for analysis of case–parental data assuming an additive genetic model, was used to estimate genetic relative risks and 95% confidence intervals for the association between LRDs and each SNP. Among women who did not take multivitamin supplements, the MTHFR 677T variant acts via the offspring's genome to increase the risk of LRDs. No association between LRDs and any fetal SNP was found among women who used multivitamin supplements. These results suggest the possibility that initiating folic acid supplementation prior to pregnancy may reduce the risk of having a LRD‐affected pregnancy, especially in women whose offspring inherit one or two copies of the MTHFR 677T variant.