Droplet Digital PCR Analysis of GSTM1 Deletion Polymorphism in Psoriatic Subjects Treated with Goeckerman Therapy
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
27639151
DOI
10.14712/18059694.2016.94
PII: 18059694.2016.94
Knihovny.cz E-resources
- Keywords
- BPDE-DNA adducts, GSTM1, Genotyping, Goeckerman therapy, Psoriasis,
- MeSH
- DNA Adducts MeSH
- Coal Tar therapeutic use MeSH
- Adult MeSH
- Genotype MeSH
- Glutathione Transferase genetics MeSH
- Keratolytic Agents therapeutic use MeSH
- Combined Modality Therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- DNA Mutational Analysis methods MeSH
- Polymerase Chain Reaction methods MeSH
- Polymorphism, Genetic MeSH
- Psoriasis genetics therapy MeSH
- Base Sequence * MeSH
- Sequence Deletion * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Ultraviolet Therapy MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA Adducts MeSH
- Coal Tar MeSH
- glutathione S-transferase M1 MeSH Browser
- Glutathione Transferase MeSH
- Keratolytic Agents MeSH
Goeckerman therapy (GT) represents an effective treatment of psoriasis including a combination of pharmaceutical grade crude coal tar (CCT) and ultraviolet irradiation (UV-R). Coal tar contains a mixture of polycyclic aromatic hydrocarbons. The best known carcinogenic polyaromate - benzo[a]pyrene is metabolized into a highly reactive benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). Glutathione S-transferase M1 (GSTM1) catalyses the conjugation of drugs, toxins and products of oxidative stress with glutathione. The aim of the study is to found possible associations between GSTM1 genotypes and the level of BPDE-DNA adducts in 46 psoriatic patients treated with GT. For genotyping, droplet digital PCR was applied. The GSTM1 copy number was normalized to β-globin reference gene. In five GSTM1*1/*1 subjects, the GSTM1 to β-globin ratio moved from 0.99 to 1.03 with a median of 1.01. GSTM1*0/*1 heterozygotes (n = 20) contained only one GSTM1 function allele which conditioned the ratio 0.47-0.53 (median 0.50). GSTM1*0/*0 individuals (n = 21) showed no amplification of the null variants because of the large deletion in GSTM1. BPDE-DNA concentrations ranged from 1.8 to 66.3 ng/µg with a median of 12.3 ng/µg. GSTM1*0/*0 and GSTM1*0/*1 genotypes showed non-significantly higher concentrations of BPDE-DNA adducts than the GSTM1*1/*1 one (12.3 and 12.4 vs 7.8 ng/µg). The non-significant relationship between BPDE-DNA adducts and GSTM1 genotypes in psoriatic patients could be associated with relatively low doses of CCT and short-term UV-R exposures used in GT.
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