GSTM1 and GSTT1 null genotypes as possible heritable factors of rosacea.
ABSTRACT 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.
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ABSTRACT: Rosacea is a common skin condition thought to be primarily an inflammatory disorder. Neutrophils, in particular, have been implicated in the inflammation associated with rosacea and mediate many of their effects through the release of reactive oxygen species. Recently, the role of reactive oxygen species in the pathophysiology of rosacea has been recognized. Many effective agents for rosacea, including topical azelaic acid and topical metronidazole, have anti-inflammatory properties. in-vitro models have demonstrated the potent antioxidant effects of azelaic acid, providing a potential mechanistic explanation for its efficacy in the treatment of rosacea.Journal of Clinical and Aesthetic Dermatology 01/2009; 2(1):26-30.
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ABSTRACT: Atopic dermatitis (AD) is a chronic pruritic skin condition affecting as much as 15% of children in industrialized countries. While the underlying pathophysiology of AD is not entirely understood, several studies have suggested that AD may mediated by oxidative stress. Glutathione S-transferases (GSTs) are a class of polymorphic enzymes that function to protect against oxidative stress. To identify any possible associations between GSTs polymorphisms and AD susceptibility, the prevalence of two specific polymorphisms -GSTM1 and GSTT1 (homozygous deletion vs. undeleted) - were quantified by multiplex PCR in 145 patients with AD and 267 healthy controls. In individuals with AD, GSTM1/GSTT1 polymorphisms were compared with family history of AD, age of disease onset, disease severity [per SCORing Atopic Dermatitis (SCORAD)], serum IgE level and presence of other allergic diseases. While the GSTM1-null genotype was found to be significantly associated with AD (P = 0.033, OR = 1.579, 95% CI = 1.037-2.403), the correlation between the GSTT1-null genotype and AD did not reach statistical significance (P = 0.577, OR = 1.125, 95% CI = 0.744-1.702). The GSTM1-null genotype was also found to be significantly associated with a childhood onset of AD, the absence of other allergic diseases, and a family history of AD. In combination, these results suggest that GSTM1 is associated with AD susceptibility in Korean subjects.International Journal of Immunogenetics 12/2010; 38(2):145-50. · 1.36 Impact Factor
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ABSTRACT: Case definitions are critical in epidemiologic research. However, modern disease indicators must now consider complex data from gene-based research along with traditional clinical parameters. Rosacea is a skin disorder with multiple signs and symptoms. In individuals, these features may be multiple or one may predominate. While studies on the epidemiology of rosacea have previously been sparse, there has been a recent increase in research activity. A broader body of epidemiological information that includes a greater variety of countries beyond Northern Europe and general population-based demographics is needed. As there are operational issues in current case definitions of rosacea subtypes-rationalization and standardization-universal consistent applications in future research is also imperative. Further improvement in disease definition combining new research information along with clinical pragmatism should increase the accuracy of rosacea case ascertainment and facilitate further epidemiological research.Journal of the American Academy of Dermatology 12/2013; 69(6S1):S27-S35. · 4.91 Impact Factor