Nejvíce citovaný článek - PubMed ID 18355300
Goeckerman therapy (GT) of psoriasis vulgaris is based on the application of crude coal tar and ultraviolet radiation. We investigated DNA damage by the number of micronucleated binucleated cells (MNBC) in lymphocytes, serum homocysteine, vitamin B12, folic acid, and two polymorphisms (C677T and A1298C) in the MTHFR gene in 35 patients with exacerbated psoriasis vulgaris classified according to the psoriasis area and severity index (PASI) score and treated by GT. The median of PASI score decreased from nineteen to five, and MNBC increased from 10 to 18‰ after GT (p < 0.001 in both cases). Correlations of MNBC with homocysteine (Spearman's rho = 0.420, p = 0.012) and vitamin B12 (rho = -0.389, p = 0.021) before the therapy were observed. Hyperhomocysteinemia was an independent predictor of genotoxicity (OR 9.91; 95% CI, 2.09-55.67; p = 0.003). Homocysteine was higher in females than in males (13 vs. 12 µmol/L, p = 0.045). In contrast, vitamin B12 levels in the females were lower than in the males (160 vs. 192 pmol/L, p = 0.047). Vitamin B12 in the females were negatively influenced by smoking status (160 pmol/L in smokers vs. 192 pmol/L in non-smokers, p = 0.025). A significantly higher MNBC was found in CC homozygous patients (A1298C polymorphism) than in AC heterozygotes (32 vs. 16‰, p = 0.005) and AA homozygotes (32 vs. 18‰, p = 0.036). Our data showed that homocysteine participates in the pathogenesis of psoriasis. Its serum levels correlated with MNBC and allowed the prediction of DNA damage to appear within GT. Both micronutrients status and homocysteine metabolic pathway contribute to the genotoxicity of GT.
- Klíčová slova
- Goeckerman therapy, folic acid, genotoxicity, homocysteine, psoriasis, vitamin B12,
- MeSH
- dehet uhelný terapeutické užití MeSH
- dospělí MeSH
- homocystein krev MeSH
- jednonukleotidový polymorfismus * MeSH
- keratolytika terapeutické užití MeSH
- kyselina listová krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylentetrahydrofolátreduktasa (NADPH2) genetika MeSH
- mikrojaderné testy MeSH
- mikroživiny krev MeSH
- poškození DNA účinky léků účinky záření MeSH
- psoriáza krev genetika patologie terapie MeSH
- terapie ultrafialovými paprsky metody MeSH
- vitamin B 12 krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dehet uhelný MeSH
- homocystein MeSH
- keratolytika MeSH
- kyselina listová MeSH
- methylentetrahydrofolátreduktasa (NADPH2) MeSH
- mikroživiny MeSH
- MTHFR protein, human MeSH Prohlížeč
- vitamin B 12 MeSH
The aim of the study was to evaluate possible association of MTHFR C677T gene polymorphism (NM_005957) with psoriasis. Genotypes of MTHFR C677T gene polymorphism were determined in a sample of 654 Caucasian (Czech) subjects. Case group (n = 410) included patients with psoriasis (plaque psoriasis diagnosed in 285 patients, other subtypes of psoriasis were observed in 125 patients). Control group (n = 244) consisted of healthy subjects without individual history of psoriasis, with similar age and gender characteristics. The MTHFR C677T polymorphism genotypes were determined by a polymerase chain reaction and a subsequent restriction analysis with HinfI. The genotypes of C(677)T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism were determined in a sample of 654 Caucasian (Czech) subjects. We proved a significant difference in genotype distribution (P(g) = 0.03) and allelic frequency (P(a) = 0.02) between psoriatic and control subjects (Table 3). The CC (the thermostabile) genotype was significantly more frequent in psoriatic patients compared to controls [OR = 1.55, 95% confidential interval (CI) = 1.12-2.15, P = 0.004814, P(corr) = 0.01]. But, a significant increase of T allele in MTHFR gene was observed in patients with positive family history of diabetes (P(a) = 0.02) and in those with a frequent tonsillitis/tonsillectomy (P(a) = 0.04). No difference was observed between patients with and without positive family history of psoriasis (P(a) = 0.251). But, when psoriatic patients were described for FHDM, FH-Ps, and PH-T simultaneously, The highest incidence of CT + TT genotypes was calculated for psoriasis patients with positive history of psoriasis and diabetes mellitus together with personal history of repeated tonsillitis/tonsillectomy compared to patients without all these three phenotypes (odds ratio = 3.17, 95% CI 1.33-7.56, P(corr) = 0.04). In conclusion, MTHFR C677T polymorphism is marginally associated with psoriasis. The T allele (thermolabile) appears to be more frequent in psoriasis patients with positive history of psoriasis and diabetes mellitus together with personal history of repeated tonsillitis/tonsillectomy. This could reflect an inborn predisposition in complex regulation in one-carbon moieties transport in psoriatic patients and therefore, MTHFR genotype can be a part of genetic background of psoriasis.
- MeSH
- alely MeSH
- diabetes mellitus 2. typu komplikace genetika MeSH
- dítě MeSH
- dospělí MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genotyp MeSH
- haplotypy genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylentetrahydrofolátreduktasa (NADPH2) genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- odds ratio MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- polymorfismus genetický genetika MeSH
- předškolní dítě MeSH
- psoriáza komplikace genetika MeSH
- rizikové faktory MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- methylentetrahydrofolátreduktasa (NADPH2) MeSH