Rosacea might be related to an increased activity of reactive oxygen species (ROS) and deficient function of the antioxidant system. Glutathione S-transferases (GSTs) play a primer role in cellular defense against electrophilic chemical species and radical oxygen species. We hypothesized that increased ROS activity or decreased antioxidant potential, possibly induced by GST gene polymorphism, might have a pathogenic role in rosacea.
The study group consisted of 45 patients with rosacea and 100 control subjects. DNA samples were isolated from blood samples using high pure polymerase chain reaction (PCR) Template preparation Kit. The GSTM1, GSTT1, and P1 polymorphisms were detected using a real-time PCR and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of rosacea were examined using logistic regression analyses to calculate odds ratios (OR) and 95% confidence intervals (CI).
GSTM1 and GSTT1 null genotypes were found to be statistically different from control (P=0.005, P=0.009, respectively), and associated with an increased risk of rosacea (OR [95% CI]: 2.84 [1.37-5.89]; OR [95% CI]: 2.68 [1.27-5.67], respectively). There was a statistically significant relationship between both null combination of the GSTM1 and GSTT1 genotype polymorphisms and rosacea (P=0.003, OR [95% CI]: 4.18 [1.57-11.13]). There were no statistically significant differences between patient and control groups for the GSTP1 Ile/Ile, Ile/Val, and Val/Val genotypes (P>0.05).
We demonstrated a significant association between the GSTT1 and/or GSTM1 null genotypes and rosacea. However, the potential role of GSTs as markers of susceptibility to rosacea needs further studies in larger patient groups.
"Besides the immunological and pathogenic mechanism, recent data suggest that oxidative stress may be an important contributor to the pathogenesis of melanocyte death (Bickers and Athar, 2006; Dell'Anna et al. 2007). The imbalance between oxidative stress and antioxidation seems to induce insufficient antioxidation protection or excess production of reactive oxygen species (ROS) (Passi et al., 1998; Beazley et al., 1999; Jimbow et al., 2001; Boisseau-Garsaud et al., 2002; Rokos et al., 2002; Koca et al., 2004; Ines et al., 2006; Yazici et al., 2006; Arican and Kurutas, 2008). The glutathione S-transferase (GST) superfamily consists of the broadly expressed phase II isoenzymes involved in defense against oxidative stress. "
[Show abstract][Hide abstract] ABSTRACT: Vitiligo is a common acquired depigmenting disorder characterized by white areas on the skin. Oxidative stress is a major pathogenesis hypothesis of vitiligo. Glutathione S-transferases (GSTs) are enzymes involved in protecting cells against chemical toxicity and stress. We hypothesized that the GSTM1- and GSTT1-null genotypes and GSTP1 polymorphisms were associated with increased risk for vitiligo. In a hospital-based case-control study of 749 vitiligo patients and 763 age- and sex-frequency-matched healthy controls, GSTM1 and GSTT1 genotypes and GSTP1 (Ile104Val, Ala113Val, Gly169Asp) polymorphisms were analyzed using the multiplex PCR and PCR-restriction fragment length polymorphism technique, respectively. We found that the GSTT1-null genotype was significantly associated with the susceptibility to vitiligo and the GSTM1-null genotype also showed a trend toward vitiligo association. We further analyzed the combined effect of GSTM1-null and GSTT1-null genotypes and showed an increased risk of developing vitiligo. By contrast, no statistically significant association was found between GSTP1 polymorphisms and vitiligo risk. These results suggest that individuals with homozygous deletion of GSTT1 and/or GSTM1 have a greater predisposition to vitiligo.
[Show abstract][Hide abstract] ABSTRACT: Rosaatsea on punetuse ja vistrikega kulgev krooniline näonaha haigus. Käesoleva töö eesmärkideks oli leida rosaatsea levimus Eesti üldrahvastikus, haiguse riskitegurid ning hinnata patsientide subjektiivset haigustunnetust sõltuvalt nende haiguskäitumisest. Uurimisgrupi moodustasid 348 juhuslikult valitud 30-77 aastast isikut üldrahvastiku hulgast ning 92 järjestikust rosaatsea tõttu dermatoloogile pöördunud patsienti vanuses 30-81 aastat. Rosaatsea sümptomite hindamiseks kasutati NRSEC (National Rosacea Society Expert Committee) diagnoosikriteeriume. Riskitegureid hinnati uuritavate poolt täidetud küsimustike alusel ja H. pylori antikehade võrdlemisel vereproovides. Depressiivsete sümptomite hindamiseks kasutati enesehinnangulist meelolu skaalat (EMS) ja subjektiivse haigustunnetuse hindamiseks visuaal-analoog-skaalat (VAS). Töö tulemused näitasid, et rosaatsea levimus Eestis ≥30-aastaste isikute hulgas on 22%, mis on kõrgem, kui senini arvatud. Rosaatsea riskiteguriteks on perekondlik eelsoodumus, päikesetundlik nahatüüp ja vanem iga. Rosaatsea raskemate vormide kujunemist soodustavad töötamine välitingimustes ning suitsetamine minevikus. Rosaatsea seos H. pylori infektsiooniga kinnitust ei leidnud. Rosaatseahaigete subjektiivne haigustunnetus ei ole seotud haiguse raskusastmega. Subjektiivselt kõrgem haigustunnetus esineb naistel ja raviasutusse pöördunud isikutel. Depressiivseid sümptome esineb sagedamini kõrgema subjektiivse haigustunnetusega patsientide hulgas. Rosacea is chronic skin condition characterized by redness, papules and pustules on the face. The aims of current study were to determine the prevalence rate of rosacea in general population in Estonia, to find risk factors of rosacea, and to observe the subjective disease perception in relation to the patients’ healthcare-seeking behaviour. The study group consisted of 348 randomly selected 30-77-year-old persons from general population and of 92 consecutive rosacea patients in age 30-81 years attended to dermatologist. For evaluating of rosacea symptoms the NRSEC (National Rosacea Society Expert Committee) diagnostic criteria were used. For assessing risk factors of rosacea a self-administered questionnaire and H. pylori antibodies detection in blood samples were used. Estonian Mood Scale (EMS) questionnaire was used for screening of depressive symptoms and visual-analogue-scale (VAS) was used for measuring of subjective disease perception. The results of current study show that the prevalence rate of rosacea is 22% among ≥30-year-old population in Estonia, that is higher than previously expected. Risk factors of rosacea are familial predisposition, sun-reactive skin type, and advanced age. Outdoor working conditions and previous smoking are the risk factors for advanced forms of rosacea. No evidence is found that rosacea is associated with exposition to H. pylori infection. Subjective disease perception of rosacea patients is not associated with the severity of the rosacea. Higher subjective disease perception was recorded among women and among healtcare-seeking study subjects. The presence of depressive symptoms is higher among rosacea patients with higher subjective disease perception. Väitekirja elektrooniline versioon ei sisalda publikatsioone.
[Show abstract][Hide abstract] ABSTRACT: Rosacea is a common inflammatory skin disorder for which the pathogenesis is unclear. Currently, there is no cure for rosacea, and it seems that standard therapies have focused mainly on minimizing inflammation.
The aim of this study is to investigate the potential efficacy, tolerability and safety profile of 1% pimecrolimus cream for the treatment of rosacea.
Twenty-five patients with papulopustular rosacea were enrolled to a randomized, single-blinded, placebo-controlled, split-face trial of pimecrolimus cream 1% consisting 4 week treatment and 2 week follow-up period. The patients were instructed to apply first the 'left side cream' labelled placebo cream (Ultrabase cream, Intendis GmbH, Berlin, Germany) to the left hemi-face then the 'right side cream' labelled 1% pimecrolimus cream (Elidel; Novartis Pharma, Nuremberg, Germany) to the right hemi-face, twice daily. They were informed to apply a standard amount of each cream with the fingertip-unit and not allowed to use any other agent concomittantly other than sunblock. Clinical evaluation and subjective severity assessment were obtained along with photographic documentation at baseline, first, second, and fourth weeks of the therapy and at the follow-up visit. Rosacea severity score for each sign of erythema, papules, pustules, oedema, and telengiectesia were graded from 0 to 3. Patients were questioned for the subjective symptoms, overall improvement on appearance and side-effects.
Twenty-four patients completed the study with an exceptional compliance and tolerable safety profile. One patient withdrew from the study due to severe flare-up reaction affecting both hemi-faces. The mean baseline total rosacea severity scores were 5.06 + 1.29 for both sides and reduced to 2.5 +/- 1.06 vs. 3.25 +/- 1.24 on pimecrolimus vs. placebo applied sides without the significance (P = 0.06). There was not any significant difference concerning each rosacea sign scores and total rosacea severity scores except for the significant improvement in erythema score and total rosacea severity score obtained on the pimecrolimus-applied hemi-face at 2nd week of therapy (P =0.01 and P = 0.03, respectively). The reduction rates of the mean subjective severity scores at 4th week were 49.77% vs. 38.89% for pimecrolimus vs. placebo, respectively, without a statistical significance (P = 0.15). Subjective symptoms responded well in 54.16% of patients concerning pimecrolimus application compared with 12.50% for the placebo application. The side-effects were mostly transient local irritations.
Our data implicated that pimecrolimus cream is not superior to placebo except for its efficacy on erythema. We believe that pimecrolimus cream can be a treatment option for rosacea patients with high erythema score for whom an initial accelerated improvement is needed. We believe further studies with topical pimecrolimus cream on larger study groups with different subtypes and severity of rosacea will clarify the potential effect of pimecrolimus cream for the treatment of rosacea.
Journal of the European Academy of Dermatology and Venereology 07/2008; 22(6):729-34. DOI:10.1111/j.1468-3083.2008.02589.x · 2.83 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.