Multiple genome analyses reveal key genes in Vitamin C and Vitamin D synthesis and transport pathways are shared

Wei Dong,Ge Lou,Ge Lou,Arnold Postlethwaite,Savannah Blackwell,Yan Jiao,Dianjun Sun,Weikuan Gu,Weikuan Gu,Cheng Tian

doi:10.1038/s41598-019-53074-9

Abstract

Vitamin C (VC) and vitamin D (VD) have been widely used as the dietary supplements and in treatment of diseases both independently and in combination. Whether there is a connection between their pathways is critical for their therapeutic applications. Using whole-genome expression profiles, we performed multiple measures of associations, networks, eQTL mappings and expressions of key genes of interest in VC and VD functions. Several key genes in their pathways were found to be associated. Gc and Rgn play important roles connecting VC and VD pathways in mice. The r values of expression levels between Gc and Rgn in mouse spleen, liver, lung, and kidney are 0.937, 0.558, 0.901, and 0.617, respectively. The expression QTLs of Gc and Rgn are mapped onto the same locations, i.e., 68–76 MB in chromosome 7 and 26–36 MB in chromosome 9. In humans, there are positive correlations between CYP27B1 and SLC23A1 expression levels in kidney (r = 0.733) and spleen (r = 0.424). SLC23A2 and RXRA are minimally associated in both mouse and human. These data indicate that pathways of VC and VD are not independent but affect each other, and this effect is different between mice and humans during VC and VD synthesis and transportation.

Highlights

Vitamin C (VC) and vitamin D (VD) are indispensable for optimal health in humans
The pathway to synthesize vitamin C is through D-glucuronate, in which L-gulonate and L-gulono-γ-lactone serve as intermediate metabolites
Since initial analysis of correlations among key genes in the VD and VC pathways showed both similarities and differences between mice and humans, we further examined in detail the correlation matrix among these genes in mouse spleen (N = 81), liver (N = 32), lung (N = 49), and kidney (N = 55) using the GeneNetwork platform with the Pearson coefficient[17]

Summary

Introduction

Vitamin C (VC) and vitamin D (VD) are indispensable for optimal health in humans. More than half a century ago, researchers found that VD deficiency could lead to rickets, and VC deficiency could lead to scurvy[1,2]. In spite of similarities between VD and VC functions in some diseases and human health, their applications in therapeutics and diet supplementation have largely been assessed independently, with little attention devoted to their potential interaction. With the help of ultraviolet B (UVB), both mouse and human body can synthesize Vitamin D3 from dehydrocholesterol (DHC). The pathway to synthesize vitamin C is through D-glucuronate, in which L-gulonate and L-gulono-γ-lactone serve as intermediate metabolites. Some primates, and guinea pigs cannot synthesize vitamin C because their Gulo gene, which produces L-gulono-γ-lactone oxidase, is mutated. In this research we chose to study the role of Gulo, Rgn, slc23a1, and Slc23a2 in VC function and the role of Vdr, Gc, Cyp24a1, Trpv[6], Cyp27b1, Cyp2r1, Dhcr[7], and Rxra in VD function

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Conclusion