Increased serum levels of Bisphenol A and Betatrophin in patients with Psoriasis

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1 Available online at ORIGINAL RESEARCH Medicine Science Intenational Medical Jounal Medicine Science 208; ( ): Inceased seum levels of Bisphenol A and Betatophin in patients with Psoiasis Suzan Demi Pektas, Niga Yilmaz 2, Ibahim Kivak 3 Mugla Sitki Kocman Univesity, Faculty Of Medicine, Depatment of Dematology, Mugla, Tukey 2 Mugla Sitki Kocman Univesity, Faculty of Medicine, Depatment of Biochemisty, Mugla, Tukey 3 Mugla Sitki Kocman Univesity, Mugla Vocational School of Highe Education, Depatment of Chemisty and Chemical Teatment Techniques, Mugla, Tukey Received 3 Januay 208; Accepted 22 Mach 208 Available online with doi: /medscience Copyight 208 by authos and Medicine Science Publishing Inc. Abstact Psoiasis is a common and seious systemic inflammatoy disease. The pupose of this study is to eseach the elationship between bisphenol A, betatophin, uocotin 3 and vitamin D levels in patients with psoiasis. Sixty patients with psoiasis (mean age, 34.±9.6 yeas) and twenty six age and gende-matched healthy individuals (mean age, 35.5 ±0.5 yeas) wee included in this study. Bisphenol A, betatophin, uocotin 3 and vitamin D levels wee assessed by using enzyme-linked immunosobent assay in all paticipants. Seum levels of bisphenol A wee detected using UPLC-ESI-MS/MS. In psoiasis patients, the median bisphenol A seum level was ng/ml (ange.), and significantly highe compaed to contols (median 0.2 ange 0.9 ng/ml) (p<0.00). The median seum level of betatophin was 270 ng/ml (ange ng/ml) in patients with psoiasis, and significantly diffeent fom the contol goup (median 98.7, ange 98.2). The median seum level of uocotin 3 was 63.3 (ange 29.) in patients with psoiasis, and it was not significantly diffeent compaed to contol goup (median 27 ange 537.9). The median seum level of vitamin D was 23.6 (ange 377), and it was significantly lowe than the contol goup (median 56.8 ange 247.) (p<0.00). A positive coelation was found between seum bisphenol A and PASI scoes in patients with psoiasis (p<0.00, =0.878). Futhemoe, uocotin positively coelated with the duation of illness (p<0.00, = 0.557). In ROC analysis, bisphenol A values geate than wee pedicted psoiasis with 88.3% sensitivity and 6.5% specificity. Betatophin levels geate than 0.89 wee pedicted psoiasis with 80% sensitivity and 69.2% specificity. We have detemined a elationship between bisphenol A, betatophin and vitamin D levels in the inflammatoy pocess in the pathophysiology of psoiasis. Bisphenol A and betatophin may be pedictive makes fo pesence of psoiasis and the disease seveity. Keywods: Psoiasis, bisphenol A, betatophin, uocotin 3, vitamin D Intoduction Psoiasis is a chonic and ecuent inflammatoy skin disease with appoximately -3% pevalence all ove the wold. It is chaacteized with hype-polifeative disode of skin in which demal-epidemal junction dives keatinocyte polifeation and development of psoiatic plaque []. Patients with psoiasis, have physical, social and psychological poblems which esult in disuptions in daily activities and pofessional esponsibilities []. Fo this eason, the teatment of the disease o the undestanding of etiopathogenesis is cucial. Although many studies have shown genetic susceptibility, epigenetic and envionmental influences ae also associated with disease [2-4]. Fo the teatment of psoiasis, initially coticosteoids ae combined with vitamin D o etinoids, and also pimay topical teatment agents ae pefeed fo mild to modeate psoiasis. Vitamin D3 seves as an immune egulato with impact on both innate and adaptive immunity, though its effects on the VDR. Vita *Coesponding Autho: Suzan Demi Pektas, Mugla Sitki Kocman Univesity, Faculty Of Medicine, Depatment of Dematology, Mugla, Tukey suzandpektas@gmail.com min D may impove outcomes by educing both local and systemic inflammatoy esponses as a esult of modulating vitamin,25- D3 inhibits polifeation of T helpe (Th) cells (consequently impaiing poduction of IL-2, tumo necosis facto α and intefeon (IFN)], as well as T helpe 7 (Th7) cells, skewing cytokine poduction towad a T helpe 2 (Th2) phenotype [5]. It has shown that the active D vitamin povided diffeentiation and polifeation of keatinocytes, the balance of immune system and apoptosis balance in the skin [6,7]. It has been expessed that lack of Psoiasis D vitamin was elated with seveity of the disease [6]. Betatophin is a ecently discoveed potein which is synthesized in the live and egulates plasma tiglyceide levels athe than egulating beta cell division on the panceas. It has been stated that betatophin deficiency causes insulin toleance and it is expeienced highly in metabolic syndome patients [6,8]. It was detemined that psoiasis might be elated to insulin toleance and its pevalence was highe in pathologies such as diabetes mellitus (DM), obesity, and metabolic syndome [7,8]. Futhemoe, it has been indicated that hypelipidemia is a isk facto fo psoiasis [8-0]. Bisphenol A belongs to a goup of substances named epoxy, which

2 doi: /medscience is fomed as a esult of pocessing plastics unde heat with vaious hadenes and catalysts. Used in many industial pocesses (ship building, metalwoking, auto epai, etc.) and health pocesses (laboatoy and dentisty), this substance can cause dematoses []. Nowadays, the most common use of bisphenol A is the poduction of polycabonate plastic blocks. These blocks ae used in the stoage of foods and beveages. Iitant contact dematitis, allegic contact dematitis, contact uticaia, and aibone contact dematitis wee stated to be developed upon contact with bisphenol A. It was also shown that this pocess stimulates cellula immune esponse with a simila effect with estadiol []. Coticotopin-eleasing facto (CRF) is a peptide epoted to have vaying levels in many diseases. High fasting blood suga, inceased epinephine, adenocoticotopic homone, aldosteone, polactin, gowth homone and estadiol; deceased cotisone and CRF elease have been shown in psoiasis [2]. Deceased coticosteoid synthesis on the skin such as uocotin has been suggested to constitute a pathogenic mechanism of psoiasis [3, 4]. To date, thee have been no publications epoting seum concentations of bisphenol A, betatophin and uocotin 3 in patients with psoiasis. To evaluate the contibution of bisphenol A, betatophin, uocotin 3 and vitamin D in the pathogenesis of psoiasis, we measued the levels of bisphenol A, betatophin, uocotin 3 and vitamin D in patients with psoiasis and detemined the elation between the paametes and clinical featues of psoiasis. Mateial and Method This study has been pefomed pospectively in Mugla Sitki Kocman Univesity Taining and Reseach Hospital Depatment of Dematology and Biochemisty between the dates 0/03/206 0/03/207 afte obtaining the appoval of Mugla Sitki Kocman Univesity Medical Faculty Hospital Ethics Committee with no. 04VIII and date 206. Study potocols wee conducted as pe Helsinki Declaation, and they had been eviewed and appoved by Ethics Committee. A total of 86 consenting subjects wee included in the study consisting of 60 patients diagnosed with psoiasis and 26 healthy contols. Age, gende, body mass index (BMI), family histoy, psoiasis peiod, psoiasis seveity, uocotin, betatophin, bisphenol A and vitamin D levels of the patients wee examined. In ode to detemine psoiasis seveity, Psoiasis Aea Seveity Index (PASI) was used. Patients with live disease, enal failue, malignancy, thyoid disease, DM, hypetension, atheoscleotic diseases, heat failue, systemic lupus eythematosus, psychiatic disease, smoking-alcoholism, substance abuse and pegnant and lactating women wee included in, and individuals below age 8 wee excluded fom ou study. Demogaphic featues, anthopometic measues wee ecoded. Psoiasis duation was obtained by self epot of the patients. Age, weight, height and body mass index [BMI; weight (kilogams)/ height (metes) 2] wee evaluated at baseline. Fasting plasma glucose (FPG) and lipid pofile [total cholesteol, tiglyceides (TG), high density lipopotein cholesteol (HDL-C), low density lipopotein cholesteol (LDL-C)] at diagnosis as metabolic analysis wee pefomed. Low density lipopotein cholesteol (LDL-C) (LDL=total cholesteol- [HDL + (TG/5)]) wee calculated as peviously descibed. Venous blood samples wee obtained fom the voluntees afte at least 8 hous fasting in the moning. Peipheal venous blood samples (0 ml) wee collected by venipunctue into tubes and centifuged fo 20 min at 2,000-3,000 pm, and seum samples wee sepaated and stoed in -80 C until the analysis. FPG was measued with Cobas 6000 Analyze (Roche Diagnostics, USA) by using the UV hexokinase method. Tiglyceide and total cholesteol was detemined with the enzymatic coloimetic assay, high density lipopotein (HDL) cholesteol was detemined with the homogenous enzymatic coloimetic assay. The level of Betatophin (Human angiopoetin-like potein 8 Elisa kit supplied by Shanghai Yehua Biological Technology Co, Ltd, China) was measued with the seum using the enzyme-linked immunosobent assay (ELISA) method. The level of Uocotin 3 was measued using an automated analyze (human uocotin-3 Elisa kit supplied by Shanghai Yehua Biological Technology Co, Ltd, China). The detemination of vitamin D level was pefomed with Human 25 dihydoxy vitamin Elisa kit (Shanghai Yehua Biological Technology Co, Ltd, China). White blood cell (WBC), neutophil and platelets counts wee measued by an automated blood cell counte (Advia 220 Hematology Analyze, Siemens Healthcae Diagnostics Deefield, IL, USA). QuEChERS Methodology In this study, a fast QuEChERS based method was pesented fo the analysis of bisphenol A in human seum at low ng/ml (ppb) level. In the compaison of QuEChERS extaction and the following SPE clean-up potocols with othe methods, a less toxic eactive was used and a simila detection limit was obtained with faste analysis. The analysis was pefomed using a tandem mass spectomete with multiple eaction monitoing (MRM) and negative electospay ionization mode. BPA D6 intenal standad was used to coect the vaiance of extaction and ionization ecovey. The calibation cuve was plotted in the ange of ng/ml. The aveage ecovey was detemined between 84.43% and 98.75%. QuEChERS methods have been the fastest, easiest, cheapest, most eliable and most obust sample pepaation techniques up to this date. This methodology has been used all aound the wold in the sample pepaation of vegetables and fuits fo the detection of pesticide esidue using GC/MS and/o LC-MS/MS. This extaction and clean-up technology can be applied effectively as an altenative to othe bulky sample pepaation pocedue. Basic equiements fo the sample matix ae easy homogenization and appopiate acetonitile extaction. Futhemoe, matix should contain >75% (w/w) wate. This atio is equied fo the pogessive clean-up of liquid potion. An additional SPE clean-up step, QuEChERS extaction pocedue was applied to human seum. This analysis design povided the detection of low level components without matix effect and deivation step. Standad SPE potocol inceased the numbe of samples and povided easie pocess due to the fact that thee wee no evapoation and deivation steps. Fo the effective extaction of a compound using QuEChERS methodology, it is necessay to constitute dispesion between acetonitile and salt-satuated wate, and to have an appopiate dispesion coefficient. Extaction and clean-up step using QuEChERS method fo bisphenol A fom human seum is 2

3 doi: /medscience appopiate fo the matix citeia and the liquid/liquid extaction citeia. Extaction of bisphenol A fom human seum One millilite of seum was put into 0 ml of centifuge tube and ml of acetonitile was added into tube. And then, it was shaken vigoously fo minute g of DisQuE pouch poducts (0.5 g CH3COONa, 0.6 g MgSO4) was added and shaken mightily fo 2 minutes, and then centifuged fo 5 minutes at 4000 pm and 0.5 ml of supenatant was sepaated into tube fo dspe clean-up. And then 90 mg magnesium sulphate, 5 mg PSA sobent and 5 mg C8 sobent wee added into tube, then wee votexed stongly fo minute, and then wee centifuged fo 5 minutes at 4000 pm. Afte SPE clean-up, final oganic eluate was dissolved with wate (50:50). The solution was filteed fom Macheey-Nagel Chomafil Xta PTFE O-20/3mm 0.20µm. UPLC-ESI-MS/MS (Wates Acquity Ulta Pefomance LC, Xevo TQ-S MS-MS) instument with an Acquity UPLC BEH.7 µm C8 Analytical column, high ph, gadient elution pogam with methanol/wate, ESI negative mode, 3000 V capillay voltages was used in bisphenol A analysis. The instument analysis paametes wee displayed in Table. Statistical Analysis Statistical Package fo the Social Sciences (SPSS) vesion 22 was used fo the statistical analysis of data. Kolmogoov Sminov test was used fo detemining distibution ange of desciptive statistics. Aveage, standad deviation (SS), median and ange values wee used fo the expession of data. The expession qualitative data was pefomed with case numbe (n) and pecentile (%). Student s t-test was used in the analysis of paametic data, while Mann Whitney-U test was used in the analysis of non-paametic data and Peason s chi-squaed test was used in the analysis of quantitative data. Peason s coelation was used fo the examination of qualitative data. ROC cuve was used fo detemining suitable cut-off values and fo the detemination of sensitivity and specificity with the cut-off values. The esults wee evaluated with 95% confidence inteval and a significance level of p <0.05. Results Sixty patients with psoiasis (29 females and 3 males) and twentysix healthy individuals (2 females and 4 males) wee included in the study. Mean age of patient and contol goups wee 34.±9.6 and 35.5±0.5 yeas, espectively (Table 2). No significant diffeences wee detemined between the goups in tems of age and gende. Similaly, no significant diffeence was found with egads to body weight, height, and body mass index (BMI) laboatoy findings in patient and contol goups (p>0.05) (Table 2). The patients had median psoiasis duation of 24.5 months (ange: 60). The family histoy of psoiasis was significantly highe in fequency fo the patients. Psoiasis patients consisted of 36 (60%)-mild psoiasis (PASI <0), and 24 (40%)-sevee psoiasis (PASI>0) patients. Bisphenol A was significantly highe in patients with psoiasis compaed to contol goup (p<0.00). The median bisphenol A seum level was ng/ml (ange.), and significantly highe compaed to contols (median 0.2 ange 0.9 ng/ml) (p<0.00) (Table2). Betatophin was found significantly highe in patients with psoiasis compaed to contol goup (p<0.00). In psoiasis patients, median uocotin 3 level was not significantly diffeent fom the contols (p>0.05). Median vitamin D seum level in psoiasis patients was significantly lowe than the contols (p<0.00) (Table 2). We found a elation between bisphenol levels and PASI scoes. Bisphenol A levels in patients with PASI 0 in the patient goup wee significantly lowe than those in PASI 0 patients (p<0.05). Thee wee no statistically significant diffeences found with egads to body weight, height, and body mass index (BMI), laboatoy findings in PASI 0 and PASI 0 psoiasis patients (p>0.05). Moeove, no coelation was found between the paametes themselves (Table 3). A positive coelation was found between uocotin and the duation of psoiasis. Also, we detemined a positive coelation between betatophin and BMI (Table 4). We found that the level of bisphenol A was highe in women with egad to gende (p<0.00). Thee wee no statistically significant diffeences found with egads to body weight, height, and body mass index (BMI), laboatoy findings in male and female patients (p>0.05). In this study, appopiate cut-off value of uocotin was detemined as 2,5 pg/ml with 86,7% sensitivity and 38,5% specificity; appopiate cut-off value of vitamin D was detemined as 82,77 ng/ml with 90,0% sensitivity and 80,8% specificity; appopiate cut-off value of betatophin was detemined as 28,65 ng/ml with 80,0% sensitivity and 69,2% specificity; and appopiate cut-off value of bisphenol A was detemined as 28,65 ng/ml with 88,3% sensitivity and 6,5% specificity fo psoiasis (Table 5, Figue ). Table. UPLC instument paametes UPLC instument paametes Column Mobile Phase A Mobile Phase B Column Oven Temp 40 C Injection Volume 5µL Acquity UPLC BEH C8 column (3.0x00mm,.7µm) %0. NH4OH in H2O %0. NH4OH in MeOH Gadient Pogam Time (min) Flow (ml/min) % Solvent A % Solvent B

4 doi: /medscience Table 2. Demogaphic and biochemical data of patient and contol goups, and compaison of uocotin, vitamin D, betatophin and bisphenol A levelsias, u(cef) values and standad, combined and expanded uncetainty values Patient (n:60) Contol (n:26) p Age, Aveage±SD 34,±9,6 35,5±0,5 0,559 Gende, n(%) Male 3 (%5,7) 4 (%53,8) 0,853 Female 29 (%48,3) 2 (%46,2) Body mass index (m2/kg), Median (Range) 23 (3,7) 22,7 (,7) 0,66 Family Histoy Yes 2 (%35) 0 0,00 No 39 (%65) 26 (%00) Psoiasis peiod (months), Median (Range) 24,5 (60) Uocotin (pg/ml), Median (Range) 63,3 (29,) 27 (537,9) 0,529 Vitamin D (ng/ml), Median (Range) 23,6 (377) 56,8 (247,) <0,00 Betatophin (ng/ml), Median (Range) 270,5 (5834,7) 98,7 (98,2) <0,00 Bisphenol A (ng/ml), Median (Range) 0,537 (,) 0,2 (0,9) <0,00 FPG (mg/dl), Median (Range) 90,5 (82) 86 (64,5) 0,335 Ceatinin (mg/dl), Median (Range) 0,8 (9,7) 0,8 (9,7) 0,53 AST (U/L), Median (Range) 8,5 (50) 8 (50) 0,537 ALT (U/L), Median (Range) 6 (93) 4 (3) 0,788 Total potein (g/dl), Median (Range) 7,2 (,7) 7, (,7) 0,302 Albumin (g/dl), Median (Range) 4,4 (,6) 4,4 (,4) 0,077 Total cholesteol(mg/dl), Median (Range) 72 (86) 70 (29) 0,77 LDL (mg/dl), Median (Range) 95,5 (4,2) 90 (94) 0,255 VLDL (mg/dl), Median (Range) 29 (50) 22 (32,4) 0,027 Tiglyceides (mg/dl), Median (Range) (267) 0 (265) 0,53 HDL (mg/dl), Median (Range) 49 (73) 5,5 (66) 0,68 WBC (/mm3), Median (Range) 7380 (79800) 6445 (8340) 0,096 Neutophilcount(/mm3), Median (Range) 430 (7500) 4260 (3920) 0,96 Leukocytecount (/mm3), Median (Range) 2420 (3680) 205 (2080) 0,06 Platelets count(/mm3), Median (Range) 245,5 (263) 238 (253) 0,825 FPG: Fasting plasma glucose, AST: aspatataminotansfeaz, ALT: alaninaminotansfeaz, LDL: Low-density lipopoteins,vldl: Vey low-density lipopoteins,hdl: High-density lipopoteins, WBC: white blood cell. Table 3. Relation of uocotin, vitamin D, betatophin and bisphenol A levels in patient and contol goups Uocotin Vitamin D Betatophin Bisphenol A Uocotin Vitamin D Betatophin Bisphenol A Uocotin Vitamin D Betatophin Bisphenol A 0,23 0,72 0,042 p 0,348 0,88 0, p p 0,07 p p p p 0.29 p Statistically significant level was detemined as p<0.05 Table 4. Relation of demogaphic chaacteistics with uocotin, vitamin D, betatophin and bisphenol A levels in patient goup Uocotin Vitamin D Betatophin Bisphenol A Age BMI Psoiasis peiod PASI 0,23 0,242 0,557 0,4 p 0,35 0,063 <0,00 0,385 0,78 0,60 0,035-0,050 p 0,74 0,222 0,79 0,705 0,02 0,30-0,026-0,060 p 0,876 0,06 0,842 0,649-0,03 0,47 0,52 0,878 p 0,432 0,26 0,247 <0,00 Statistically significant level was detemined as p<0.05 4

5 doi: /medscience Table 5. Aea, cut-off, sensitivityandspecificity of uocotin, vitamin D, betatophinandbisphenol A levels Asymptotic 95% ConfidenceInteval Test ResultVaiable(s) Aea Cut-off Sensitivite Spesifite p LoweBound UppeBound Uocotin 0,457 2,5 86,7 38,5 0,529 0,298 0,66 Vitamin D 0,074 82,77 90,0 80,8 <0,00 0,08 0,30 Betatophin 0,89 28,65 80,0 69,2 <0,00 0,78 0,920 Bisphenol A 0,764 0,23 88,3 6,5 <0,00 0,649 0,879 Statisticallysignificantlevel is assumed as p<0.05 vaiance in vitamin D eceptos o genes in linkage disequilibium with the vitamin D eceptos gene, may be a isk facto fo development of psoiasis [23]. In ou study, it was detemined that vitamin D level was significantly lowe in patient goup, and it was not detemined to be associated with PASI scoe and othe paametes. We conside that vitamin D deficiency contibutes in psoiasis by disupting immunity, keatinocyte diffeentiation and apoptosis balance. In pevious studies, the eseaches stated that patients with psoiasis had a 3% inceased pobability of multiple scleosis compaed to the geneal population. They detemined a elation between psoiasis with multiple scleosis due to inceasing systemic inflammation. Systemic inflammation leads to insulin esistance and subsequently tigges endothelial cell dysfunction, pomoting cadiovascula disease [24-26]. Mattozzi and fiends detemined a coelation between vitamin D and clinical seveity of psoiasis calculated with PASI scoe. And also, they stated that the level of vitamin D is in coelation with the clinical seveity of psoiasis [27]. Sevee-to-modeate psoiasis effects ae defined as a PASI scoe >0. In pevious studies, psoiasis, especially the modeate-sevee fom, was detemined to behave as a systemic inflammatoy disease associated with metabolic syndome [28]. Figue. ROC cuves of uocotin, vitamin D, betatophin and bisphenol A Discussion Although psoiasis is ecognized as a disease involving the immune system, its etiology is not known exactly [4-6]. Vitamin D is a key modulato in inflammatoy pocess [7]. It has been shown that the active metabolite of vitamin D shows an anti-inflammatoy effect of human monocyte/macophages and inflammatoy pofile and egulates the expession and poduction of many po-inflammatoy cytokines (TNF-α, IL -, IL-6 and IL-8) [8,9]. With vitamin D, cytokine-induced diffeentiation of T-cells, inceased polifeation and inceased poduction of immunoglobulin may be expeienced. Inceased inflammatoy effects due to vitamin D deficiency have been associated with psoiasis in some studies. It has been demonstated that Vitamin D causes the stimulation of in vito keatinocyte polifeation at low concentations and inhibition ( 0-8 M) at highe concentations [20,2]. Wadhwa and fiends stated that administation of vitamin D supplements contibuted in educing inflammation and evesion of some changes occuing in psoiatic lesion [20]. It was shown that decease in mrna expession caused by pomoto polymophism of vitamin D eceptos affected cutaneous baie and the development of psoiatic lesions [9,22]. A pevious study epoted that thee was a significant diffeence in allele fequencies and vitamin D eceptos genotypes between nomal contols and psoiasis patients, especially with ealy onset. This suggests that allelic Cujeias and fiends stated in thei study that betatophin level was significantly highe in individuals with metabolic syndome, obesity, and impaied lipid pofile and glucose toleance [6]. Fenzl and fiends have shown a significant coelation between betatophin level and plasma atheogenic lipids in mobid obese patients and patients with type 2 DM, howeve, no elation was detemined with contol goup [29]. Fu and fiends has shown a positive coelation between betatophin and BMI [30]. It has been detemined that the pevalence of psoiasis inceases in metabolic diseases, pimaily in hypelipidemia [8,9,2,28]. It was detemined in ou study that betatophin level was significantly highe in patients with psoiasis, showed positive coelation with BMI in patient goup; and it was not associated with othe demogaphic data, PASI scoe, and othe paametes. Psoiasis is an immunological eaction in which tissue eaction occus as a esult of sevee inflammatoy component and abnomal keatinocyte diffeentiation. It is developed in the consequence of activation of T cells migating to skin though the activation of immune system elements such as keatinocytes and denditic cells, and some cytokines [3]. Aytekin and fiends have shown that effect mechanism of Bisphenol A on the skin is developed due to the stimulation of cellula immune esponse []. In this study, bisphenol was studied with highly efficient and highly sensitive UPLC-ESI-MS/MS. It was detemined in ou study that Bisphenol A levels inceased in psoiasis patients, bisphenol A levels inceased with inceasing PASI scoe; and they wee not associated with othe demogaphic data and othe paametes apat 5

6 doi: /medscience fom gende. We think that bisphenol A causes psoiasis as a esult of the cellula immune eaction it poduces. Since immunological eactions ae moe common in female patients, we conside that Bisphenol A level inceases in female psoiasis patients. Uocotin is one of the substances affecting CRF ecepto, and it is stated to be found on the skin [32,33]. Singh and fiends stated that uocotin levels deceased in psoiasis, and this caused inceased pemeability as a esult of mast cell deganulation though othodomic stimulation of the tigeminal neve in acute psychological stess [3]. Zangeneh and fiends have epoted that most stess homones incease due to inceased stess in psoiasis, and CRF and cotisone elease have not changed. The eseaches well descibed the po-inflammation ole of CRF which is synthesized by cutaneous cells and immune cells in human skin, such as CRF-induced activation of mast cells in the phenomenon of stess elated of cutaneous inflammatoy diseases [34]. Moeove, mast cells expess CRF eceptos, and thei activation causes selective elease of cytokines and othe poinflammatoy mediatos [2]. It has been stated that incease in endogenous glucocoticoids and CRF/uocotin decease at the tissue level may disupt pemeability baie and cause psoiasis [35]. CRF is up-egulated in psoiasis, as the stess-integating peptide which involved in the inflamed tissues of patients with psoiasis [34]. It was detemined in ou study that uocotin level did not change in psoiasis, and it was not associated with age, BMI and disease seveity. Nevetheless, a positive coelation was detemined between uocotin level and psoiasis peiod. Although homones wee elated to stess, we conside that this shows uocotin inceases with adaptive mechanisms in a long time athe than acutely. In liteatue, no studies wee detemined that evaluate the elationship between vitamin D, bisphenol A, betatophin and uocotin levels in psoiasis. Also, no coelation was detemined among these paametes with each othe in ou study. This suggests that these fou paametes may play a ole in psoiasis though sepaate ways. Also, the possibility that these makes may be effective on attack fequency and lesion development in psoiasis led to the conclusion that it does not povide any opinions fo its pesence in the etiology. In liteatue, no studies wee detemined that evaluate the sensitivity and specificity of vitamin D, bisphenol A, betatophin and uocotin levels in psoiasis. It was consideed in ou study that vitamin D, bisphenol A and betatophin levels wee effective on thei own since they had high sensitivity and specificity in psoiasis; while uocotin level was not consideed to be effective on its own since it had high sensitivity and low specificity. This bings us to the conclusion that these ecently descibed biomakes may play a ole in clinical use in the nea futue. Conclusion Ou study shed light on the psoiasis by investigating the elationship between bisphenol A, betatophin, uocotin 3 and D vitamin. We suggest that inceased levels of bisphenol A, betatophin and deceased level of D vitamin can be used as a pedictive make of psoiasis and disease seveity. Competing inteests The authos declae that they have no competing inteest Financial Disclosue The financial suppot fo this study was povided by the investigatos themselves. Refeences. Melikoglu M. Sleep Quality and its Association with Disease Seveity in Psoiasis. Euasian J Med. 207;49(2): Kuma P, James W. Psoiasis, Plaque. StatPeals. Teasue Island Balci DD, Balci A, Kaazinci S, Uca E, Iyigun U, Yalcin F, and fiends. Inceased caotid atey intima-media thickness and impaied endothelial function in psoiasis. J Eu Acad Dematol Veneeol. 2009;23(): Neimann AL, Shin DB, Wang X, Magolis DJ, Toxel AB, Gelfand JM. Pevalence of cadiovascula isk factos in patients with psoiasis. 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