Meta-analysis of vitamin D receptor polymorphisms and psoriasis risk.

BACKGROUND: Vitamin D receptor (VDR) gene polymorphisms have been studied as candidate variants that affect psoriasis risk. However, results have been conflicting. METHODS: We reviewed studies on VDR polymorphisms and psoriasis risk published to October 1, 2011, and quantitatively summarized associations of the most widely studied variants (FokI, TaqI, ApaI, BsmI) using meta-analysis. Associations were measured using random-effect odds ratios (ORs) combined with 95% confidence intervals (CIs). RESULTS: Eleven eligible studies, encompassing 1106 cases and 1209 controls, were retrieved from electronic databases and included in this review. The results were heterogeneous, which may be partly explained by small sample bias, the phenomenon of winner's curse, and differences among populations. For FokI and ApaI polymorphisms, we did not find any evidence of association. A borderline allelic association was found for the BsmI B variant after exclusion of the earliest significant report (OR = 0.81, 95% CI 0.68-0.98; P = 0.04, inconsistency index [I2] = 12.7%). Among Caucasian subjects, the TaqI t allele was nominally associated with psoriasis risk (OR = 0.77, 95% CI 0.64-0.97; P = 0.012, I (2) = 0), with homozygous carriers (tt vs. TT, OR = 0.59, 95% CI 0.39-0.90; P = 0.01, I2 = 0) and recessive model (tt vs. Tt + TT, OR = 0.66, 95% CI 0.44-0.98; P = 0.04, I2 = 0) as protective factors. None of these associations persisted after adjustment for multiple comparisons. No publication bias was detected in this meta-analysis. CONCLUSIONS: No genetic variant examined in the VDR gene showed a robust and reproducible association with risk for psoriasis. Any association that may exist is likely to be weak and potentially restricted to specific populations.

Polymorphisms of vitamin D receptor gene in the population of eastern Croatia with psoriasis vulgaris and diabetes mellitus.

The aim of this study was to evaluate the possible association between polymorphisms in the Vitamin D receptor gene (VDR gene) and tendency for development of psoriasis vulgaris and diabetes mellitus in the population of Slavonia, which is a region in the Eastern Croatia. In order to conduct the mentioned evaluation the restriction fragment length polymorphisms (ApaI, BsmI and TaqI) in the Vitamin D receptor gene were researched in three groups of patients: patients suffering only from psoriasis vulgaris, patients suffering only from diabetes mellitus, and patients suffering at the same time from both diseases. Four most common genotypes were found in all standardized control patients: triple heterozygotes BbAaTt (in 29.3% of the studied patients), bbAaTT (in 18.6% of the studied patients), bbaaTT (in 12.9% of the studied patients) and BbAATt (in 8.6% of the studied patients). Three most common VDR 3'-RFLP haplotypes determined in this study were: three-component baT, Bat and bAT haplotype. Results of the Hardy-Weinberg equilibrium showed presence of BsmI polymorphism genotype frequencies disequilibrium in the group of patients suffering from psoriasis and ApaI polymorphism in the group of patients suffering from both diseases. According to the same statistical test all conditions for TaqI polymorphism genotype frequency were fulfilled in all groups of studied patients. There was no significant difference in distribution of BsmI, ApaI or TaqI polymorphism genotype frequencies between control patients and any of the subgroup of studied patients. In studied population none of analysed polymorphisms individually was associated with the risk of development of psoriasis, diabetes or combined phenotype.

Lack of association of vitamin D receptor gene 3'-haplotypes with psoriasis in Croatian patients.

Cis-acting regulatory variants in biologically relevant pathways and target tissues are a common source of phenotypic variations and individual disease susceptibility. In the skin, vitamin D receptor (VDR) is a master regulator of epidermal barrier function, inflammation, stem cell proliferation and microbial defense; therefore, we tested whether VDR 3'-regulatory haplotypes, a portion of which affect VDR transcriptional efficiency, allelic symmetry and mRNA turnover, were associated with psoriasis vulgaris. For this purpose, three VDR tag polymorphisms that capture most of the variability of the VDR 3'-regulatory element (rs1544410, rs7975232 and rs731236) were genotyped by the polymerase chain reaction restriction fragment length polymorphism method in 180 Caucasian patients with chronic plaque psoriasis and 366 ethnically matched, healthy controls of the Croatian origin. We found no evidence of association for any of the selected polymorphisms. Similarly, none of the 3'-VDR restriction haplotypes were associated with the risk for development of psoriasis in Croatian patients. These results show that neither VDR 3'-restriction polymorphisms nor common 3'-regulatory haplotypes contribute to psoriasis risk in the Croatian population.

Vitamin D endocrine system and psoriasis vulgaris--review of the literature.

Vitamin D exerts its physiological functions on calcium and bone metabolism in humans through the active metabolite 1,25-dihydroxyvitamin D3(1,25(OH)2D3). The other spectrum of vitamin D activities includes important effects on cellular proliferation, differentiation and the immune system. These effects are mediated through the intracellularly located vitamin D receptor (VDR). VDR is a member of the steroid, estrogen and retinoid receptor gene family of proteins that mediate transcriptional activities of the respective ligands. The VDR complex binds in the nucleus to the vitamin D responsive element on the gene. Several polymorphisms of the vitamin D receptor (VDR) gene have been described including FokI in exon 2, BsmI and ApaI in intron 8 and TaqI in exon 9. Alterations in vitamin D-1,25 (OH)2D3 levels and polymorphisms of VDR gene have been shown to be associated with several malignant or autoimmune diseases such as sclerosis multiplex, breast cancer, diabetes mellitus, malignant melanoma, and psoriasis vulgaris. The effects of VDR gene polymorphisms including immunomodulation, stimulation of cellular differentiation and inhibition of proliferation make it a possible candidate for therapy of psoriasis as well as for the psoriasis gene modification. The objective of this article is to present the state-of-the-art in the VDR gene polymorphism research in psoriasis vulgaris.

Epidemiology of acquired bullous diseases in Eastern Croatia: a retrospective prewar to postwar study.

The purpose of this study was to evaluate the epidemiology of bullous diseases (BD) in eastern Croatia during a ten-year period (1986-1990/1992-1996), and to estimate the effect of prolonged exposure to traumatic events during the war in Croatia on the prevalence and incidence of acquired BD. The files of all BD patients hospitalized at Department of Dermatology and Venereology, Osijek University Hospital, during the periods from January 1986 to December 1990 and from January 1992 to December 1996 were collected and analyzed with regard to personal data, history of the disease including age, sex and onset of symptoms, clinical diagnosis, laboratory findings, and associated illness. Forty-five patients were newly diagnosed with BD over the ten-year period. During the 1986-1990 period, 19 patients with BD represented 0.89% of 2133 patients admitted to our Department. During the 1992-1996 period, 26 newly diagnosed patients with BD represented 1.27% of 2050 patients treated at our Department. Females were more affected than males. The most common clinical variant was pemphigus vulgaris, occurring frequently in the middle-aged population. All our patients were exposed to prolonged stressful war conditions during the 1992-1996 period, therefore, we speculate that extended emotional stress may have triggered the onset of the disease.

Buschke's scleredema and concomitant diseases: report of five cases and literature review.

Scleredema adultorum or Buschke's scleredema is a rare disorder that belongs to the group of mucinoses. Diffuse, sudden swelling, hardening and induration of the skin can occur in children and younger women as well as in older men. The dermis is thickened because of the increased collagen glycosylation, like that in diabetic stiff skin syndrome. The face is most often involved. In older persons the trunk is usually first involved. There is relative sparing of the extremities, with no distal or Raynaud's phenomenon. Eosinophilic fasciitis, scleromyxedema, associated gammopathy, and other forms of edema and mucin deposition must be excluded on differential diagnosis. Antibiotics, sometimes high doses of intravenous penicillin, systemic corticosteroids, systemic PUVA and PUVA bath therapy seem most promising for the management of the disorder. Our patients were aged 27, 60, 64, 69 and 72 years, with typical skin lesions, thus that term "adultorum" does not appear to fit well.

Historical development of local therapy of psoriasis vulgaris.

Throughout the history people have used various remedies for the treatment of psoriasis. Some of them were bizarre, some ineffective and harmful, and some have survived until today and are still in use. Salicylic acid, anthralin, coal tar, corticosteroids, vitamin D3 analogues, retinoids must be mentioned as remarkably effective ones. Phototherapy and laser therapy are both promising techniques, as well as immunomodulators. Underlying mechanisms of psoriasis and mode of action of therapeutics that have been elucidated over the time allowed for the development of more potent and promising therapy of psoriasis.

Trigger factors in childhood psoriasis and vitiligo.

Psoriasis and vitiligo are very common skin disorders that may have a profound impact upon the affected individuals; the etiology of both diseases includes genetic factors and triggers, which could be endogenous or exogenous. Two groups of children population consisting of 153 patients suffering from skin disorder (65 with vitiligo and 88 with psoriasis) have been examined at the Department of Dermatovenerology, University Hospital Osijek, during three years period. Basic methods of data collection were: questionnaire, clinically examination and histological proven diagnosis. The aim of this investigation were to determine the most common triggers, which play a role at onset of disease among young patients with vitiligo and psoriasis, and to establish familial distribution among both groups of patients. The results of investigations showed that the onset of vitiligo was mostly connected with psychological factors (56.9%), but the most frequently trigger in childhood psoriasis was inflammatory focus (38.6%). According to morphologic patterns the authors separated two groups of patients among psoriatics: group I with plaque psoriasis, which pointed the inflammatory focus and physical trauma as trigger before onset of disease (each 25.0%) and group II with psoriasis guttata and inflammatory focus as trigger at even 62.5% cases. Familial distribution among psoriatic children was 55.6%, and among children with vitiligo only 16.9%. Ours children patients showed significantly disparity in structure of triggers according diagnosis and gender distributions and about familial occurrence. Also some difference has been established according to age of onset between psoriasis and vitiligo at early childhood.

Syphilitic aneurysm: case report.

Tertiary syphilis is a rare, slowly progressive inflammatory disease that becomes clinically visible years after initial infection. Although it can affect any organ in the body, it shows a predilection for the cardiovascular and nervous systems. Today, however, cardiovascular syphilis is a medical curiosity because the disease can successfully be treated with antibiotics in its early phase. We present a case of a 43-year-old male patient with a syphilitic aneurysm of the descendent aorta and our choice of treatment.

Epidemiology of dermatomycosis in the eastern Croatia--today and yesterday.

The aim of our investigation was to compare the distribution of dermatomycosis species in Eastern Croatia between two different periods: first period from 1997-2001 year, and second period from 1986-88 year. The outpatients from Department of Dermatovenerology University Hospital "Osijek" with confirmed diagnosis infection. Tinea, were selected on the basis o age, gender, localization and dermatomycosis species. During the first period (1997-2001) among 75,691 outpatients Tinea infection was confirmed in 558 (0.73%), while in the second period among 47,832 outpatients there were 126 (0.26%) cases with Tinea, what showed significant increase of fungal infections among population this region. According the age and gender in both periods predominant population were under of the age 16(40.14%: 41.26%), and female population was predominant (58.60% and 57.14%) in comparison to males (41.39% and 42.85%). The most frequent localization of lesions in period I were cutis glabrae (47.31%), palms and soles (31.36%), capitis (17.38%) and unguis (9.31%) and isolated species were as followed: Trichophyton (39.06%), Microsporum (31.72%) and Candida (28.13%) species. In period II the most frequent localization were palms and soles (40.47%), cutis glabrae (36.50%), capitis (12.69%) and unguis (10.31%). The isolated species in this period were: Trichophyton (80.15%), Candida (12.69%) and Microsporum (4.76%) species. From the data collected during two different periods we can observe 1) increase of fungal infection generally in our region; 2) significant changes in causative species (increase of Microsporum and Candida species infection, but Trichophyton spp still remain the first causative agent); and 3) changes in the localization of lesions.

The role of the low energy diet in psoriasis vulgaris treatment.

The aim of the present study was to determine whether and how the low energy diet acts on reduce of plasma lipids and clinical features of moderate non pustular psoriasis vulgaris. The investigation carried out in Clinical hospital Osijek, at Department of Dermatology as well as at Nutrition Department, included 82 in-patients, aged 46 to 65 (mean age 53.7 +/- 7.9), which had at least a 10-year history of the skin disorders. 42 participants (22 men and 20 women) in addition to usual topical therapy (neutral bland ointments twice daily), received a low energy diet during four weeks. Controls (40 participants: 22 men and 18 women) received only topical therapy with regular hospital food. Total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol in blood, body weight and clinical features were measured at the beginning of investigation and after four weeks. After four weeks participants on low energy diet showed statistical significantly decreasing of serum lipids in relation to control group as well as significantly decreasing of clinical skin disorders. On contrary there were no significant changes on body weight between both groups of participants. Results of our study suggest that low energy diet could be important adjuvant factor in the prevention and treatment of moderate non pustular psoriasis.