Evaluation of proton-coupled folate transporter (SLC46A1) polymorphisms as risk factors for neural tube defects and oral clefts

Julia E VanderMeer; Tonia C Carter; Faith Pangilinan; Adam Mitchell; Emma Kurnat-Thoma; Peadar N Kirke; James F Troendle; Anne M Molloy; Ronald G Munger; Marcia L Feldkamp; Maria A Mansilla; James L Mills; Jeff C Murray; Lawrence C Brody

doi:10.1002/ajmg.a.37539

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Evaluation of proton-coupled folate transporter (SLC46A1) polymorphisms as risk factors for neural tube defects and oral clefts

Journal article

Open access

Peer reviewed

Evaluation of proton-coupled folate transporter (SLC46A1) polymorphisms as risk factors for neural tube defects and oral clefts

Julia E VanderMeer, Tonia C Carter, Faith Pangilinan, Adam Mitchell, Emma Kurnat-Thoma, Peadar N Kirke, James F Troendle, Anne M Molloy, Ronald G Munger, Marcia L Feldkamp, …

American journal of medical genetics. Part A, Vol.170A(4), pp.1007-1016

04/2016

DOI: 10.1002/ajmg.a.37539

PMCID: PMC6205290

PMID: 26789141

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https://www.ncbi.nlm.nih.gov/pmc/articles/6205290View

Open Access

Abstract

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.

Cleft Lip - genetics

Genetic Association Studies

Proton-Coupled Folate Transporter - genetics

Gene Frequency

Humans

Risk Factors

Alleles

Neural Tube Defects - genetics

Genotype

Polymorphism, Single Nucleotide

Case-Control Studies

Details

Title: Subtitle: Evaluation of proton-coupled folate transporter (SLC46A1) polymorphisms as risk factors for neural tube defects and oral clefts
Creators: Julia E VanderMeer - Section of Molecular Pathogenesis, Medical Genomics Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland
Tonia C Carter - Division of Intramural Population Health Research, Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Faith Pangilinan - Section of Molecular Pathogenesis, Medical Genomics Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland
Adam Mitchell - Section of Molecular Pathogenesis, Medical Genomics Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland
Emma Kurnat-Thoma - Section of Molecular Pathogenesis, Medical Genomics Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland
Peadar N Kirke - Unit of Child Health Epidemiology, Health Research Board, Dublin, Ireland
James F Troendle - Office of Biostatistics Research, Department of Health and Human Services, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
Anne M Molloy - Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland
Ronald G Munger - Department of Nutrition, Dietetics and Food Sciences, Utah State University, Logan, Utah
Marcia L Feldkamp - Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah
Maria A Mansilla - Division of Neonatology, Department of Pediatrics, University of Iowa, Iowa City, Iowa
James L Mills - Division of Intramural Population Health Research, Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
Jeff C Murray - Division of Neonatology, Department of Pediatrics, University of Iowa, Iowa City, Iowa
Lawrence C Brody - Section of Molecular Pathogenesis, Medical Genomics Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part A, Vol.170A(4), pp.1007-1016
DOI: 10.1002/ajmg.a.37539
PMID: 26789141
PMCID: PMC6205290
NLM abbreviation: Am J Med Genet A
ISSN: 1552-4825
eISSN: 1552-4833
Publisher: United States
Grant note: Intramural NIH HHS Z01 HD002502-15 / Intramural NIH HHS
Language: English
Date published: 04/2016
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
Record Identifier: 9984025447002771

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