ABSTRACT
BACKGROUND: Previous studies showed the role of vitamin D (Vit D) on the progression of chronic urticaria. To the best of our knowledge, there are no other results regarding the contribution of single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes in chronic urticaria (CU). AIM: In the present study, we investigated the Vit pathway and the association between VDR and VDBP gene polymorphisms and CU risk in Iranian population. METHODS: All participating individuals in the present study were evaluated for serum Vit D and VDBP concentration VDR rs1544410 and rs2228570 and VDBP rs7041using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The associations of studied analytes and three SNPs with clinical and laboratory outcomes were investigated in CU patients. RESULTS: Patients with CU showed lower Vit D compared to controls (19.26 ± 1.26 vs. 31.72 ± 7.14 ng/ml, P-value = 0.006). There was a significant correlation between Vit D levels and urticaria activity score. Serum VDBP was significantly higher in CU patients than controls (1317.3 ± 183.71 vs. 395.77 ± 12.96 µg/ml, P-value <0.0001) and had a positive correlation to progression of CU. The A allele of this polymorphism might be a potential risk factor for progression of CU [odds ratio 4.3434, 95% confidence interval (1.7331-10.8852), Z-statistic = 3.133, P-value = 0.0017]. CONCLUSION: In summary, this study demonstrated that change in Vit D pathway in the level of gene or protein may be a risk factor for progression of CU.
Subject(s)
Calcitriol/blood , Urticaria/blood , Urticaria/genetics , Vitamin D-Binding Protein/blood , Adult , Case-Control Studies , Chronic Disease , Disease Progression , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Receptors, Calcitriol/genetics , Risk Factors , Vitamin D-Binding Protein/genetics , Young AdultABSTRACT
Trimethylamine N-oxide (TMAO), a common metabolite in animals and humans, can induce changes in the expression or conformation of heat shock proteins. It has also been introduced as a risk factor for atherosclerosis and a biomarker for kidney problems. On the other hand, increased levels of heat shock proteins 60 and 70 KDa are associated with increased atherosclerosis risk. This study was therefore designed to evaluate the possible effect(s) of TMAO on the expression of HSP60 and GRP78 at the mRNA and protein levels. Murine macrophage J774A.1 cells were treated with micromolar concentrations of TMAO and 4-phenylbutyric acid (4-PBA), a chemical chaperon, for different time intervals. Tunicamycin was also used as a control for induction of endoplasmic reticulum stress. Tunicamycin greatly increased both mRNA and protein levels of GRP78. Similarly but to a lesser extent compared to tunicamycin, TMAO also increased mRNA and protein levels of GRP78 in a dose and time-dependent manner. In contrast, 4-PBA failed to induce any changes. Similar to GRP78, HSP60 was also increased only at mRNA level in TMAO treated cells. 4-PBA also increased HSP60 mRNA levels, whereas, tunicamycin did not show any effect on either protein or mRNA levels of HSP60. Since both heat shock proteins are stress inducible and the elevation of GRP78 is a hallmark for endoplasmic reticulum stress induction, it can be concluded that TMAO may induce endoplasmic reticulum stress or may act through elevation of these heat shock proteins.
Subject(s)
Chaperonin 60/biosynthesis , Endoplasmic Reticulum Stress/drug effects , HSP70 Heat-Shock Proteins/biosynthesis , Heat-Shock Proteins/biosynthesis , Macrophages/metabolism , Membrane Proteins/biosynthesis , Methylamines/pharmacology , Mitochondrial Proteins/biosynthesis , Animals , Butylamines/pharmacology , Cell Line , Chaperonin 60/genetics , Endoplasmic Reticulum Chaperone BiP , HSP70 Heat-Shock Proteins/genetics , Heat-Shock Proteins/genetics , Macrophages/drug effects , Membrane Proteins/genetics , Mice , Mitochondrial Proteins/genetics , RNA, Messenger/biosynthesis , Tunicamycin/pharmacologySubject(s)
Delivery of Health Care, Integrated , Obesity/psychology , Patient Care Team , Adolescent , Child , Cross-Sectional Studies , Female , Germany , Humans , Male , Obesity/epidemiology , Risk FactorsABSTRACT
Over the past two decades, obesity in children has been increasing worldwide, leading to serious complications. The treatment for childhood obesity remains largely ineffective; therefore preventive measures are crucial. The prevalence of obesity depends on the BMI-percentiles used. Recent BMI-percentiles may underestimate the problem. Currently, the only representative cross-sectional BMI-data are obtained at the school entry examination. These data reveal certain risk groups (migrants, low socioeconomic status). More representative longitudinal data are needed to study the progression of obesity during childhood. Our obesity clinic provides multidisciplinary therapy programs (group or individual) and is also focused on the diagnosis and treatment of comorbidity, especially of the metabolic syndrome. Almost 60% of our severely obese patients are already affected. The molecular diagnosis of rare monogenetic or syndromal forms of obesity may be helpful in providing additional support for these patients. In general, most obesity programs are successful only in families without severe psychosocial problems and with motivation for lifestyle changes. This can be expected in only 3% of our families. Therefore, a substantial societal effort is needed to facilitate prevention for all children, and effective therapies have to be tailored depending on biological and psychosocial risk factors.
