过氧化氢酶基因启动子和 5'-非翻译区变异导致白癜风中基因表达和酶活性的改变。

The catalase gene promoter and 5'-untranslated region variants lead to altered gene expression and enzyme activity in vitiligo.

机构信息

Department of Biochemistry, Faculty of Science, Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390002, India.

出版信息

Br J Dermatol. 2017 Dec;177(6):1590-1600. doi: 10.1111/bjd.15681. Epub 2017 Nov 22.

DOI:10.1111/bjd.15681

PMID:28542879

Abstract

BACKGROUND

Oxidative stress is considered to be the initial event in the course of vitiligo. The enzyme catalase (CAT) is mainly involved in cellular defence against oxidizing agents through detoxifying H O .

OBJECTIVES

The aims were (i) to assess erythrocyte CAT enzyme activity and lipid peroxidation (LPO) levels as well as CAT mRNA expression in skin and blood; (ii) to investigate CAT gene promoter rs7943316, rs1001179, 5'-untranslated region rs1049982, and exon (rs17886350, rs11032709, rs17880442, rs35677492) polymorphisms; and (iii) to perform genotype/haplotype-phenotype correlation analyses in patients with vitiligo and controls from Gujarat.

METHODS

CAT activity and LPO levels were measured spectrophotometrically. CAT mRNA levels were estimated using real-time polymerase chain reaction (PCR) by the SYBR Green method. Single-nucleotide polymorphism genotyping was performed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system-PCR analyses.

RESULTS

Patients with vitiligo showed significantly decreased CAT mRNA expression in lesional and nonlesional skin and in blood, with reduced CAT activity compared with that of controls. CAT -89A/T and -20T/C polymorphisms were significantly associated with patients, especially with active and generalized vitiligo, whereas no association was observed for -262G/A and exon polymorphisms. The A T C haplotype with variant alleles was found to be associated with 6·4-fold risk of vitiligo. Genotype/haplotype-phenotype correlation analyses revealed that individuals with susceptible genotypes/haplotype for CAT -89A/T and -20T/C polymorphisms showed significantly decreased CAT mRNA/activity, and only -89A/T polymorphisms showed significantly increased LPO levels compared with wild-type genotypes/haplotype.

CONCLUSIONS

The present study proposes the crucial role of CAT and its allelic variants in oxidative stress-mediated pathogenesis of vitiligo.

摘要

背景

氧化应激被认为是白癜风病程中的初始事件。过氧化氢酶 (CAT) 主要通过解毒 H O 参与细胞对抗氧化剂。

目的

本研究旨在（i）评估红细胞 CAT 酶活性和脂质过氧化 (LPO) 水平以及皮肤和血液中的 CAT mRNA 表达；（ii）研究 CAT 基因启动子 rs7943316、rs1001179、5'-非翻译区 rs1049982 以及外显子 (rs17886350、rs11032709、rs17880442、rs35677492) 多态性；（iii）在来自古吉拉特邦的白癜风患者和对照组中进行基因型/单倍型-表型相关性分析。

方法

采用分光光度法测量 CAT 活性和 LPO 水平。采用实时聚合酶链反应 (PCR) 通过 SYBR Green 法估计 CAT mRNA 水平。采用 PCR 限制性片段长度多态性和扩增受阻突变系统-PCR 分析进行单核苷酸多态性基因分型。

结果

与对照组相比，白癜风患者皮损和非皮损皮肤及血液中的 CAT mRNA 表达明显降低，CAT 活性也降低。CAT-89A/T 和-20T/C 多态性与患者显著相关，尤其是与活动期和泛发性白癜风相关，而-262G/A 和外显子多态性与患者无相关性。携带变异等位基因的 A T C 单倍型与白癜风的 6.4 倍风险相关。基因型/单倍型-表型相关性分析显示，CAT-89A/T 和-20T/C 多态性易感基因型/单倍型个体的 CAT mRNA/活性明显降低，只有-89A/T 多态性与野生型基因型/单倍型相比，LPO 水平明显升高。