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  • Clinical Research Article
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The role of vitamin D receptor gene polymorphism in the development of necrotizing enterocolitis

Pediatric Research volume 94, pages 275–279 (2023)Cite this article

Abstract

Background

Vitamin D and its receptor (VDR) effects on the gastrointestinal system are among its most critical multisystemic effects.

Methods

This study aimed to reveal that VDR gene polymorphisms may constitute a risk factor for necrotizing enterocolitis (NEC). VDR Fok1-Bsm1-Apa single-nucleotide polymorphisms were analyzed in the NEC group (n = 74) and the control group (n = 147). Among 1112 babies at and below 36 weeks of gestational age who were hospitalized between January 2013 and December 2016 with a diagnosis of prematurity, 74 of a total of 148 patients who developed NEC during follow-up (NEC group) were included in the study. When NEC was diagnosed according to clinical and radiological findings and staged using Modified Bell criteria, 9 (12.1%) of 74 babies were stage 1A, 13 (17.5%) stage 1B, and 5 (6.7%) stage 2A, 33 (44.5%) stage 2B, 7 (9.4%) stage 3A, 7 (9.4%) stage 3B. Of 964 babies who did not develop NEC during follow-up, 147 were included as the control group in the study. Genotyping of VDR polymorphisms was assayed by real-time PCR. From 221 premature babies in the NEC and control groups, 2 ml peripheral blood was taken appropriately and meticulously into an EDTA tube. DNA was isolated from these blood samples. DNA amplification was performed using a thermal cycler (Applied Biosystems GeneAmp PCR System 9600).

Results

When the two groups were compared in terms of the prevalence of VDR Fok1 C/T genotype, it was found that TT genotype increased the risk of NEC by 2.697 times, and there was a significant relationship between TT genotype and the risk of NEC (p = 0.041). Multivariable logistic regression analysis was performed in terms of gestational age, birth weight, VDR gene polymorphism data between NEC and the control group. According to the analysis results, TT polymorphism, increased the risk of disease 4.5 times (p = 0.033).

Conclusion

Fok 1 C > T polymorphism in the VDR gene plays a role in the development of NEC. Identifying the risk groups by detecting gene polymorphisms that cause increased susceptibility to NEC may assist in the follow-up of these patients and in making early treatment decisions for them.

Impact

  • In this study examining the non-bone effects of the genetic differences in vitamin D metabolism in premature babies, Fok 1 polymorphism has been observed to be an essential risk factor for NEC.

  • This is the first study in our country that has investigated the relationship between VDR gene polymorphism and necrotizing enterocolitis among the Turkish population.

  • Identifying the risk groups by detecting gene polymorphisms that cause increased susceptibility to NEC may assist in the monitoring of these patients and in making early treatment decisions for them.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank Professor Mehmet Orman for his contribution to the statistical analysis of this study.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Ege University Hospital, Bornova, Izmir, 35100, Turkey

    Dogan Barut

  2. Department of Pediatrics, Division of Neonatology, Ege University Hospital, Bornova, Izmir, 35100, Turkey

    Mete Akisu, Ozge Altun Koroglu, Demet Terek, Firat Ergin, Mehmet Yalaz & Nilgun Kultursay

  3. Department of Medical Genetics, Ege University Hospital, Bornova, Izmir, 35100, Turkey

    Huseyin Onay

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Contributions

D.B. and M.A. conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript, final approval of the version to be published. D.B., O.A.K., D.T., and F.E. contributed to the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript, drafting the article or revising it critically for important intellectual content; and final approval of the version to be published. H.O., M.Y., and N.K. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content, substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Dogan Barut.

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The authors declare no competing interests.

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Permission to participate in the study was obtained from the families and the center where the study was conducted.

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Barut, D., Akisu, M., Koroglu, O.A. et al. The role of vitamin D receptor gene polymorphism in the development of necrotizing enterocolitis. Pediatr Res 94, 275–279 (2023). https://doi.org/10.1038/s41390-022-02426-9

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