Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene

Durmus Doğan; Eda Gül Özcan; Dilek Ülker Çakır; Fatma Sılan

doi:10.3389/fendo.2023.1281112

Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene

Front Endocrinol (Lausanne). 2023 Dec 7:14:1281112. doi: 10.3389/fendo.2023.1281112. eCollection 2023.

Authors

Durmus Doğan¹, Eda Gül Özcan², Dilek Ülker Çakır³, Fatma Sılan⁴

Affiliations

¹ Department of Pediatric Medicine, Division of Pediatric Endocrinology, Çanakkale Onsekiz Mart University, Çanakkale, Türkiye.
² Department of Pediatric Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Türkiye.
³ Department of Biochemistry, Çanakkale Onsekiz Mart University, Çanakkale, Türkiye.
⁴ Department of Medical Genetics, Çanakkale Onsekiz Mart University, Çanakkale, Türkiye.

Abstract

Introduction: Vitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele.

Methods: A cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups.

Results: Participants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035).

Conclusion: Individuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

Keywords: Rs4588; gC gene; polymorphism; serum 25-hydroxyvitamin D; urinary excretion; vitamin D binding protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Cross-Sectional Studies
Female
Gene Frequency
Genotype
Humans
Male
Polymorphism, Genetic*
Vitamin D-Binding Protein* / blood
Vitamin D-Binding Protein* / genetics
Vitamin D-Binding Protein* / urine

Substances

Vitamin D-Binding Protein
GC protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. It was supported by Çanakkale Onsekiz Mart University Scientific Research Projects Coordination Unit as a project numbered BTSA-2021-3603.