Catalase (CAT) promoter and 5′-UTR genetic variants lead to its altered expression and activity in vitiligo

Summary

Background

Oxidative stress is considered to be the initial event during the course of vitiligo. Catalase is mainly involved in the defense against oxidizing agents in the cell through detoxifying H₂O₂.

Objectives

Aims of the present study were 1) to assess the erythrocyte catalase activity and LPO levels, as well as CAT mRNA expression in skin and blood; 2) to investigate CAT promoter rs7943316, rs1001179; 5′-UTR rs1049982 and exon (rs17886350, rs11032709, rs17880442, rs35677492) polymorphisms and; 3) to perform genotype-phenotype/ haplotype correlation analyses, in vitiligo patients and controls from Gujarat.

Methods

Catalase activity and lipid peroxidation levels were measured spectrophotometrically. CAT mRNA levels were estimated using Real-time PCR by SYBR-Green method. SNP genotyping was performed using PCR-RFLP/ ARMS-PCR methods.

Results

Vitiligo patients showed significantly decreased CAT mRNA-expression in lesional, non-lesional skin and in blood with reduced catalase activity compared to 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. ‘A_-262T_-89C_-20′ 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 -89 A/T and -20 T/C polymorphisms showed significantly decreased catalase mRNA/activity, and only -89 A/T polymorphisms showed significantly increased lipid peroxidation levels, as compared to wild type genotypes/ haplotype.

Conclusions

In conclusion, the present study proposes the crucial role of catalase and its allelic variants in oxidative stress mediated pathogenesis of vitiligo.

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