Role of cytochrome P450 for vitamin D metabolisms in patients with neurodegenerative disorders

Asako Kakimoto; Hiromu Ogura; Midori Suenaga; Takayasu Mishima; Shinsuke Fujioka; Shinji Ouma; Yoichi Matsunaga; Yoshio Tsuboi

doi:10.1016/j.prdoa.2022.100162

Role of cytochrome P450 for vitamin D metabolisms in patients with neurodegenerative disorders

Clin Park Relat Disord. 2022 Aug 27:7:100162. doi: 10.1016/j.prdoa.2022.100162. eCollection 2022.

Authors

Asako Kakimoto^{1

2}, Hiromu Ogura¹, Midori Suenaga³, Takayasu Mishima¹, Shinsuke Fujioka¹, Shinji Ouma¹, Yoichi Matsunaga¹, Yoshio Tsuboi¹

Affiliations

¹ Department of Neurology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
² Department of Neurology, Konishi Daiichi Hospital, Fukuoka, Japan.
³ Department of Medical Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima-Bunri University, Tokushima, Japan.

Abstract

Introduction: We previously reported lower serum 25-hydroxyvitamin D concentrations in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Multiple system atrophy (MSA) compared to healthy controls (HC), whereas 1,25-di-hydroxyvitamin D levels were solely lower in MSA patients. We investigate serum concentrations of P450 involved in Vitamin D(VD) hydroxylation to clarify the responsible hydroxylase for the low serum concentrations of VD metabolites.

Methods: A total of 79 individuals were enrolled including 20 HC, 20 AD, 19 PD and 20 MSA patients. The serum concentrations of P450 involved in VD hydroxylation were assayed by ELISA. The data were analyzed by the nonparametric Kruskal-Wallis test between groups.

Results: Though CYP2R1 and CYP27A1 mediate 25-hydroxylation for VD, CYP2R1 is the main hydroxylase, and CYP27A1 is also involved in VD synthesis. CYP2R1 concentrations showed no differences among groups, while lower CYP27A1 concentrations were found in PD (p < 0.05) and MSA (p < 0.005) compared to HC and differences between AD and MSA (p < 0.05), however no differences between PD and MSA. CYP27B1 is the main 1α-hydroxylase for 25-hydroxyvitamin D and showed differences between HC and PD (p < 0.05), between HC and MSA (p < 0.005) and between PD and MSA (p = 0.055). CYP24A1, which inactivate 1,25-di-hydroxyvitamin D, showed no differences among groups.

Conclusions: CYP27A1 might affect VD synthesis and cause low 25-hydroxyvitamin D levels in AD, PD and MSA patients. Low 1,25-di-hydroxyvitamin D levels in MSA patients might be caused by impaired feedback mediated by CYP27B1.

Keywords: 1,25(OH)2D, 1,25-dihydroxyvitamin D3; 25(OH)D, 25-hydroxyvitamin D3; AD, Alzheimer's disease; Alzheimer’s disease; CYP, cytochrome P450; CYP24A1; CYP27A1; CYP27B; CYP2R1; HC, Healthy control; MSA, Multiple system atrophy; Multiple system atrophy; PD, Parkinson's disease; Parkinson’s disease; Vitamin D.