VDR 多态性、基因表达与北印度人群麻风病患者维生素 D 水平的关系。

VDR polymorphism, gene expression and vitamin D levels in leprosy patients from North Indian population.

机构信息

Stanley Browne Laboratory, The Leprosy Mission Trust India, The Leprosy Mission Community Hospital, Nand Nagari, New Delhi, Delhi, India.

出版信息

PLoS Negl Trop Dis. 2018 Nov 27;12(11):e0006823. doi: 10.1371/journal.pntd.0006823. eCollection 2018 Nov.

DOI:10.1371/journal.pntd.0006823

PMID:30481178

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6286024/

Abstract

BACKGROUND

Leprosy is a chronic infectious disease caused by Mycobacterium leprae and mainly affects skin, peripheral nerves. Vitamin D receptor (VDR) gene polymorphism has been found to be associated with leprosy. Vitamin D has been shown to control several host immunomodulating properties through VDR gene. Vitamin D deficiency was also found to be linked to an increased risk for several infections and metabolic diseases.

OBJECTIVE

In the present study, we investigated the association of VDR gene polymorphism, mRNA gene expression of VDR and the vitamin D levels with leprosy and its reactional states.

METHODOLOGY

A total of 305 leprosy patients consisting of tuberculoid (TT), borderline tuberculoid (BT), borderline lepromatous (BL), lepromatous leprosy (LL), as well as 200 healthy controls were enrolled in the study. We identified single nucleotide polymorphisms (SNPs) of VDR Taq1, Fok1 and Apa1, as well as the expression of VDR mRNA gene using PCR-based restriction fragment length polymorphism (RFLP) analysis and real-time PCR respectively. We also performed ELISA to measure vitamin D levels.

RESULT

We observed that SNP of VDR gene (Fok1 and Taq1) are associated with the leprosy disease. The allelic frequency distribution of T and t allele (p = 0.0037), F and f allele (p = 0.0024) was significantly higher in leprosy patients and healthy controls. ff genotype of Fok1 was found to be associated with leprosy patients [p = 0.0004; OR (95% CI) 3.148 (1.662-5.965)]. The recessive model of Fok1 genotype was also found to be significantly associated in leprosy patients in comparison to healthy controls [p = 0.00004; OR (95% CI) 2.85 (1.56-5.22)]. Leprosy patients are significantly associated with t-F-a haplotype. Further, VDR gene expression was found to be lower in non-reaction group compared to that of reaction group of leprosy and healthy controls. Paradoxically, we noted no difference in the levels of vitamin D between leprosy patients and healthy controls.

CONCLUSION

Blood levels of vitamin D do not play any role in clinical manifestations of any forms of leprosy. ff genotype of Fok1 and tt genotype of Taq1 was found to be associated with leprosy per se. Association of t-F-a haplotype with leprosy was found to be significant and could be used as a genetic marker to identify individuals at high risk for developing leprosy. VDR gene expression was lower in TT/BT and BL/LL groups of leprosy in comparison to that of healthy controls.

摘要

背景

麻风病是一种由麻风分枝杆菌引起的慢性传染病，主要影响皮肤和周围神经。维生素 D 受体（VDR）基因多态性与麻风病有关。维生素 D 已被证明通过 VDR 基因控制多种宿主免疫调节特性。维生素 D 缺乏也与多种感染和代谢性疾病的风险增加有关。

目的

本研究旨在探讨 VDR 基因多态性、VDRmRNA 基因表达和维生素 D 水平与麻风病及其反应状态的关系。

方法

共纳入 305 例麻风病患者（结核样型[T]、边界结核样型[BT]、边界偏瘤型[BL]、瘤型[LL]）和 200 例健康对照者。采用 PCR 限制性片段长度多态性（RFLP）分析和实时 PCR 分别鉴定 VDR Taq1、Fok1 和 Apa1 单核苷酸多态性（SNP）及 VDRmRNA 基因表达。采用 ELISA 法测定维生素 D 水平。

结果

我们发现 VDR 基因（Fok1 和 Taq1）的 SNP 与麻风病有关。麻风病患者和健康对照组 T 和 t 等位基因（p=0.0037）、F 和 f 等位基因（p=0.0024）的等位基因频率分布差异有统计学意义。Fok1 的 ff 基因型与麻风病患者有关（p=0.0004；OR（95%CI）3.148（1.662-5.965））。与健康对照组相比，Fok1 基因型的隐性模型在麻风病患者中也有显著相关性（p=0.00004；OR（95%CI）2.85（1.56-5.22））。麻风病患者与 t-F-a 单倍型显著相关。此外，与健康对照组相比，非反应组麻风病患者 VDR 基因表达较低。但奇怪的是，我们没有发现麻风病患者与健康对照组之间维生素 D 水平有差异。