Genetic Variation in the Sodium-dependent Vitamin C Transporters, SLC23A1, and SLC23A2 and Risk for Preterm Delivery
Abstract
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.
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Some common SLC23A1 polymorphisms are associated with increased risk of Crohn's disease, non-Hodgkin lymphoma, preterm delivery, and aggressive periodontitis.
“Some common SLC23A1 polymorphisms were found to be associated with an increased risk of Crohn’s disease [86], non-Hodgkin lymphoma [87], preterm delivery [84], and aggressive periodontitis [88].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [84]
Common variations of SLC23A2 are linked to preterm delivery.
“Common variations of SLC23A2 were linked to increased or decreased risk of gastric cancer depending on a discrete genotype [85,90], decreased risk of colorectal adenocarcinoma [91], HPV16-positive head and neck cancer [92], increased risk of bladder cancer [93], non-Hodgkin lymphoma [87], chronic lymphocytic leukemia [94], preterm delivery [84], open-angle glaucoma [95], and acute coronary syndrom”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [84]
SNPs of SLC23A1 are more common in African and African-American populations than others, while SNPs of Slc23A2 are of similar frequency in Caucasian and African populations.
“These SNPs are more common in the African and African-American populations over others, while SNPs of Slc23A2 are of a similar frequency in the Caucasian and African populations [80,82,84].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [84]
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- Authors
- Erichsen, H. C., Engel, S. A. M., Eck, P. K., Welch, R., Yeager, M., Levine, M., Siega-Riz, A. M., Olshan, A. F., & Chanock, S. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Erichsen, Hans Christian
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-12-15
- Volume
- 163
- Issue
- 3
- Pages
- 245-254
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- OpenAlex
- W2159750423
- Cited by
- 79
- References
- 45
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 5 · 2013: 12 · 2012: 5
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- preterm birth, SLC23A1, SLC23A2, vitamin C transporter, single nucleotide polymorphisms, genetic susceptibility, haplotypes, pregnancy, vitamin C intake
- MeSH terms
- Adult, Alleles, Ascorbic Acid, Black or African American, Female, Haplotypes, Humans, North Carolina, Pregnancy, Risk Factors, Genetic Variation, Case-Control Studies, Polymorphism, Single Nucleotide, Symporters, Organic Anion Transporters, Sodium-Dependent, White People, Premature Birth, Sodium-Coupled Vitamin C Transporters
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