title: Droplet Digital PCR Analysis of GSTM1 Deletion Polymorphism in Psoriatic Subjects Treated with Goeckerman Therapy.
abstract: 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.
authors.affiliation: Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic. beranek@lfhk.cuni.cz.|Institute of Clinical Biochemistry and Diagnostics, Charles University Hospital and Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic. beranek@lfhk.cuni.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Beránek
authors.affiliation: Institute of Hygiene and Preventive Medicine, Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Fiala
authors.affiliation: Institute of Pathological Physiology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Kremláček
authors.affiliation: Institute of Clinical Immunology and Allergology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.
authors.forename: Ctirad
authors.initials: C
authors.lastname: Andrýs
authors.affiliation: Clinic of Dermal and Venereal Diseases, Charles University Hospital Hradec Králové, Hradec Králové, Czech Republic.
authors.forename: Květoslava
authors.initials: K
authors.lastname: Hamáková
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University Hospital and Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Palička
authors.affiliation: Institute of Pathological Physiology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Borská
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D003033:Coal Tar / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018736:DNA Adducts; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007641:Keratolytic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D011565:Psoriasis / Q000235:genetics* / Q000628:therapy*; D017384:Sequence Deletion; D014467:Ultraviolet Therapy; D055815:Young Adult
chemical_list: D003033:Coal Tar; D018736:DNA Adducts; D005982:Glutathione Transferase; D007641:Keratolytic Agents
keywords: BPDE-DNA adducts; GSTM1; Genotyping; Goeckerman therapy; Psoriasis