遗传对尿维生素 D 结合蛋白排泄和血清水平的影响：以 GC 基因 rs4588 C>A 多态性为重点。

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

机构信息

Department of Pediatric Medicine, Division of Pediatric Endocrinology, Çanakkale Onsekiz Mart University, Çanakkale, Türkiye.

Department of Pediatric Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Türkiye.

出版信息

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

DOI:10.3389/fendo.2023.1281112

PMID:38144557

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10740204/

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.

摘要

简介

维生素 D 结合蛋白 (VDBP) 在维生素 D 转运和代谢中发挥着关键作用。GC 基因编码 VDBP 的 rs4588-A 多态性与血清 VDBP 和 25-羟维生素 D（25OHD）水平的改变有关。然而，这些影响的机制尚不清楚。我们旨在研究携带和不携带 rs4588-A 等位基因的个体中尿 VDBP 排泄与血清 VDBP 和 25OHD 水平之间的关系。

方法

对 109 名儿童（平均年龄：11.96 岁）进行横断面研究，以探讨 rs4588-A 对维生素 D 代谢和尿 VDBP 排泄的影响。生化分析测定血清 25OHD 和 VDBP 水平以及尿 VDBP 与肌酐的比值（u-VDBP/Cr）。使用 LightSNiP 检测法对 rs4588 SNP 进行基因分型。统计分析包括相关性、线性回归和等位基因组之间的比较。

结果

携带 rs4588-A 等位基因的参与者血清 25OHD 水平较非携带者低（中位数（IQR）：11.85（3.5）vs. 12.86（4.9），p=0.023）。然而，血清 VDBP 水平（rs4588-A 为 126.34±59.3，非 rs4588-A 为 136.49±51.3，p=0.141）或 u-VDBP/Cr（中位数（IQR）：rs4588-A 为 0.4（0.35），非 rs4588-A 为 0.386（0.43），p=0.189）在两个等位基因组之间无统计学差异。仅在 rs4588-A 携带者中发现 u-VDBP/Cr 与血清 VDBP 水平呈显著负相关（r=-0.367，p=0.024）。在非携带者或整个队列中未观察到这种相关性。线性回归分析证实了 rs4588-A 携带者 u-VDBP/Cr 对血清 VDBP 水平的影响（B=-0.269，t=-2.185，p=0.035）。