American Journal of Epidemiology Advance Access originally published online on December 15, 2005
American Journal of Epidemiology 2006 163(3):245-254; doi:10.1093/aje/kwj035
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Original Contribution |
Genetic Variation in the Sodium-dependent Vitamin C Transporters, SLC23A1, and SLC23A2 and Risk for Preterm Delivery
1 Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD
2 Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY
3 Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
4 Core Genotyping Facility, Advanced Technology Center, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
5 Department of Maternal and Child Health, School of Public Health, University of North Carolina, Chapel Hill, NC
6 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC
Correspondence to Dr. Stephen J. Chanock, Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 (e-mail: sc83a{at}nih.gov).
Vitamin C has been the focus of epidemiologic investigation in preterm delivery (<37 weeks' gestation), which is a leading cause of neonatal mortality and birth-related morbidity. There are two sodium-dependent membrane transporters encoded by SLC23A1 and SLC23A2, which have key roles in human vitamin C metabolism and which control dietary uptake, reabsorption, and tissue distribution of vitamin C. Using maternal DNA, the authors evaluated common single-nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2 in a nested case-control analysis of the Pregnancy, Infection, and Nutrition Study (1995–2000) cohort. Of the associations observed for both haplotypes in SLC23A1 and individual SNPs in SLC23A2, the most robust finding is with an intron 2 variant in SLC23A2. Heterozygotes and homozygotes for this variant had a 1.7-fold (95% confidence interval: 0.9, 3.3) and a 2.7-fold (95% confidence interval: 1.2, 6.3) elevation in the risk of spontaneous preterm birth, respectively. Semi-Bayesian hierarchical regression analysis, which simultaneously adjusted for multiple SNPs within the same gene, gave comparable results. The authors' findings link genetic variants in the vitamin C transporters to spontaneous preterm birth, which may explain previous dietary associations. If the findings from this study are confirmed, they may serve as the foundation for genetic risk assessment of nutritional pathways in preterm birth.
ascorbic acid; polymorphism, single nucleotide; premature birth; rupture, spontaneous
Abbreviations: CI, confidence interval; OR, odds ratio; SNP, single-nucleotide polymorphism
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