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Evaluation of proton‐coupled folate transporter ( SLC46A1 ) polymorphisms as risk factors for neural tube defects and oral clefts
Author(s) -
VanderMeer Julia E.,
Carter Tonia C.,
Pangilinan Faith,
Mitchell Adam,
KurnatThoma Emma,
Kirke Peadar N.,
Troendle James F.,
Molloy Anne M.,
Munger Ronald G.,
Feldkamp Marcia L.,
Mansilla Maria A.,
Mills James L.,
Murray Jeff C.,
Brody Lawrence C.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37539
Subject(s) - minor allele frequency , odds ratio , allele , neural tube , genotype , medicine , etiology , genetics , population , single nucleotide polymorphism , pregnancy , neural tube defect , case control study , allele frequency , gastroenterology , biology , fetus , gene , embryo , environmental health
Many folate‐related genes have been investigated for possible causal roles in neural tube defects (NTDs) and oral clefts. However, no previous reports have examined the major gene responsible for folate uptake, the proton‐coupled folate transporter ( SLC46A1 ). We tested for association between these birth defects and single nucleotide polymorphisms in the SLC46A1 gene. The NTD study population included 549 complete and incomplete case‐family triads, and 999 controls from Ireland. The oral clefts study population comprised a sample from Utah (495 complete and incomplete case‐family triads and 551 controls) and 221 Filipino multiplex cleft families. There was suggestive evidence of increased NTD case risk with the rs17719944 minor allele (odds ratio (OR): 1.29; 95% confidence intervals (CI): [1.00–1.67]), and decreased maternal risk of an NTD pregnancy with the rs4795436 minor allele (OR: 0.62; [0.39–0.99]). In the Utah sample, the rs739439 minor allele was associated with decreased case risk for cleft lip with cleft palate (genotype relative risk (GRR): 0.56 [0.32–0.98]). Additionally, the rs2239907 minor allele was associated with decreased case risk for cleft lip with cleft palate in several models, and with cleft palate only in a recessive model (OR: 0.41; [0.20–0.85]). These associations did not remain statistically significant after correcting for multiple hypothesis testing. Nominal associations between SLC46A1 polymorphisms and both Irish NTDs and oral clefts in the Utah population suggest some role in the etiology of these birth defects, but further investigation in other populations is needed. © 2016 Wiley Periodicals, Inc.