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

BackgroundOxidative 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 H2O2. ObjectivesThe aims were (i) to assess erythrocyte CAT enzyme activity and lipid peroxidation (LPO) levels as well as CATmRNA 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. MethodsCAT activity and LPO levels were measured spectrophotometrically. CATmRNA 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. ResultsPatients with vitiligo showed significantly decreased CATmRNA 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(-262)T(-89)C(-20) haplotype with variant alleles was found to be associated with 64-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 CATmRNA/activity, and only -89A/T polymorphisms showed significantly increased LPO levels compared with wild-type genotypes/haplotype. ConclusionsThe present study proposes the crucial role of CAT and its allelic variants in oxidative stress-mediated pathogenesis of vitiligo. What's already known about this topic? Oxidative stress is considered to be the initial event during the course of vitiligo. Epidermal H2O2 accumulation is associated with low epidermal catalase (CAT) levels in vitiligo. There is no association of the CAT exon 9 T/C polymorphism with Gujarat patients with vitiligo. What does this study add? Patients with vitiligo showed significantly decreased CAT mRNA expression in lesional and nonlesional skin and in blood, with reduced CAT activity.CAT -89A/T and -20T/C polymorphisms were associated with patients from Gujarat with active and generalized vitiligo. Susceptible genotypes/haplotype for CAT -89A/T and -20T/C polymorphisms showed significantly decreased CAT mRNA and CAT activity, while the -89A/T polymorphism showed significantly increased lipid peroxidation levels. What is the translational message? Low levels/activity of antioxidant enzymes such as CAT in patients with vitiligo emphasizes the role of oxidative stress-mediated melanocyte damage. Outcomes of this study could be translated into the development of personalized medicines on the basis of an individual's genotypes/haplotype for key antioxidant enzymes, which could lead to better management of disease, in addition to predicting susceptibility to vitiligo. Linked Comment: Bohm. Br J Dermatol 2017; 177:1477. Plain language summary available online Respond to this article