Anais
Brasileiros
de
Dermatologia
www.anaisdedermatologia.org.br
INVESTIGATION
Association
of
CYP2J2
polymorphism
with
susceptibility
to
psoriasis
in
Turkish
population:
a
case---control
study
夽,夽夽
Yıldız
Hayran
a,∗,
Nuran
Allı
a,
Pınar ˙Incel
Uysal
a,
Tuba
C
¸andar
baDepartmentofDermatology,AnkaraNumuneTrainingandResearchHospital,Ankara,Turkey
bDepartmentofMedicalBiochemistry,UfukUniversityFacultyofMedicine,Ankara,Turkey
Received10September2018;accepted19April2019 Availableonline10December2019
KEYWORDS Diseasesusceptibility; Psoriasis; Polymorphism; Singlenucleotide Abstract
Background: Cytochrome P450 2J2 is mostly expressed in extrahepatic tissues; it
metab-olizes arachidonic acid to epoxyeicosatrienoic acids, with various cardio protective and anti-inflammatoryeffects.CYP2J2polymorphismhasbeenidentifiedasariskfactorfor cardio-vasculardiseases,butitsassociationwithpsoriasisremainsunknown.
Objective: ToevaluateCYP2J2polymorphismasariskfactorforpsoriasisintheTurkish
popu-lation.
Methods: Therewere94patientswithpsoriasisand100age-andsex-matchedhealthycontrols
includedinthestudy.Detaileddemographicandclinicalcharacteristicswererecorded,and Pso-riasisAreaandSeverityIndex(PASI)scoreswerecalculatedforpsoriasispatients.Venousblood sampleswerecollectedfromalltheparticipantsandCYP2J250G>T(rs890293)polymorphism wasanalyzedusingpolymerasechainreaction(PCR).
Results: BothTalleleandTT+GTgenotype frequencieswereincreasedinpsoriasisvulgaris
patientscomparedtothecontrolgroup(p=0.024andp=0.029respectively,OR=2.82,95%CI: 1.11---7.15)NoassociationbetweenCYP2J2polymorphismandclinicalfeaturesofpsoriasiswas identified.
Studylimitations: Alimitednumberofpatientswereincludedinthestudy.
Conclusion: CYP2J250G>T(rs890293)polymorphismwasassociatedwithanincreasedriskfor
PsVintheTurkishpopulation.
©2019SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/). 夽 Howtocitethisarticle:HayranY,AllıN,UysalP˙I,C¸andarT.AssociationofCYP2J2polymorphismwithsusceptibilitytopsoriasisinTurkish population:acase---controlstudy.AnBrasDermatol.2020;95:25---31.
夽夽StudyconductedattheDepartmentofDermatology,AnkaraNumuneTrainingandResearchHospital,Ankara,Turkey. ∗Correspondingauthor.
E-mail:yildizkantarci@yahoo.com(Y.Hayran).
https://doi.org/10.1016/j.abd.2019.04.006
0365-0596/©2019SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).
Introduction
Psoriasis is a chronic inflammatory skin disease charac-terizedby sharply demarcated erythematouspapules and plaqueswithsilveryscales.However,theprevalencevaries widely between studies (0---11.8%) according to age, gen-der, and race; psoriasis is thought to affect about 2% of thegeneralpopulation.1Psoriasis affectsmenandwomen
equally.Althoughitcanstartatanyage,twoagepeaksin theincidencehavebeenobserved: thefirstinsecondand third decade, and the second in fifth and sixth decade.2
Skin, nail, or jointinvolvement can beseen in up to50% ofthepatients,andtheassociationofpsoriasiswithmany systemic disorderssuch as cardiovascular diseases, infec-tions,metabolicdisorders,kidneydiseases,gastrointestinal diseases, and malignancies is well documented.3---5 The
etiopathogenesisofthediseaseisnotwellunderstood. Pso-riasisiscategorizedasamultifactorialdiseasewithgenetic, environmental, immunological, and inflammatory factors thatcontributetopathogenesisofthedisease.6
Inflamma-tion,bothlesionalandsystemic,isanimportantfeatureof psoriasis.Manystudiesinvestigatingsystemicinflammation in psoriasis revealed that markers of inflammation (espe-cially C-reactive protein, tumor necrosis factor [TNF]-␣, intracellular adhesion molecule [ICAM]-1, E-selectin, and interleukin [IL]-1, IL-6, IL-10) are increased in psoriatic patients,creatingasystemicinflammatorystatethatcould leadtocomorbiditieslikecardiovasculardiseases.7
Cytochrome P450 (CYP) enzymes are hemoproteins mostlylocatedintheendoplasmicreticulum (ER)or mito-chondrialmembraneinhumans.ThemainfunctionofCYPs istometabolize drugs,non-drugxenobiotics, and endobi-otics such as fatty acids, steroids and steroid hormones, bileacids,VitaminD,prostaglandins,andarachidonicacid (AA).8---10AAismetabolizedtofourepoxyeicosatrienoicacids
(EETs) 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. EETs promote vascular relaxation, have an anti-inflammatory effectin endothelium,and acardioprotective effect dur-ingischemic events.11,12 Besides their favorableeffect on
cardiovascular and inflammatory diseases, EETs may also promote proliferation, migration, and survival in tumor cells.13CYP2J2---CYPisoformmostlyexpressedintheliver,
heart, small intestine, kidney, and brain --- is one of the main CYPsconvertingAA toEETs.14 CYP2J2polymorphism
hasbeeninvestigatedincardiovasculardiseases, ischemic stroke,andAlzheimer’sdisease,andithasbeenshown to increasesusceptibilitytothesediseases.15---18
TheaimofthisstudywastoinvestigateCYP2J2 polymor-phisminpsoriasis,achronicinflammatoryskindiseasethat canbeaccompaniedbycardiovasculardiseases.
Materials
and
Methods
Studypopulation
Inthepresentstudy,94clinicallyorhistopathologically diag-nosed psoriasis patient admitted to the Ankara Numune TrainingandResearchHospitalbetween January2015and July 2016. As a control group, 100 age and sex-matched patientsadmittedtothedermatologyoutpatientclinicwith a dermatological disease other than psoriasis --- with no
history of any chronic inflammatory disease --- were recruited. Demographic characteristics of both psoriasis patients andthe controlgroup,and clinical features (dis-easesubtype,duration,severity,familyhistory,treatments, history of psoriatic arthritis, and involvement of special localizationsuchasthescalp,flexuralareas,andnails)of the diseasewererecorded. Psoriaticarthritiswas investi-gatedinallpatients.Historyofpsoriaticarthritiswasnoted andpatientswithactivearthralgiaorarthritiswerereferred totherheumatologydepartmentforadefinitivediagnosisof psoriaticarthritis.Children(age<18),pregnantand breast-feeding participants, and participants with history of any immunologicalorinflammatorydiseaseswereexcludedfrom thestudy.
The study wasapproved bylocal ethics committee (E-15-612)andallparticipantsgavewritteninformedconsent priortothestudy.
Polymorphismanalysis
Primerdesignwascarriedoutforthepolymerasechain reac-tion(PCR)amplificationoftheCYP2J2-50G>Tpolymorphism region,sothatthelocusofthepolymorphismwasata prox-imityof150bpfrombothendsofthePCRamplicon.Thisis becauseasequencingkitwasused,whichreads150bpfrom both ends. Beforethe primerswere ordered, the authors addedspecificsequencesofabout30nucleotidesto5ends oftheprimers,tomaketheampliconssuitableforindexed sequencingonIlluminaplatforms.Table1summarizesPCR primerpairs,locusspecificsequences,andsequencesadded for index PCR. DNA samples were obtained with the iso-lationfrom200Lbloodsamplesfromeachindividual,by usingaQIAampDNABloodMiniKit(QiagenInc.).PCRswere carriedoutonisolatedDNAsamplesbyusingthedesigned primersandthereactionswerecheckedbyusing2%agarose gelelectrophoresis.AsecondPCRforindexingpurposeswas conductedtoaddindexsequencestotheamplicons,inorder toachievemultiplexinginnext-genesequencing;foreachof thesamples,adifferentcombinationofindexprimerswas used. IndexingPCR reactions were also checked by using 2% agarose gel electrophoresis. Equal volumesof indexed PCRreactionsweremixedtoobtainaPCRpool,whichhad alltheampliconsofallsamples.ThePCRpoolwaspurified byusingaNucleoFast® 96PCRkit(Macherey-NagelGmbH). The purifiedpool wasquantified byusing amicro volume spectrophotometeranddilutedaccordingtothe recommen-dationsofIlluminaInc.Next-genesequencingofthesamples wascarriedoutby usingtheMiseqsystem (IlluminaInc.). Genotyping of the samples wasachievedas the datawas analyzedonIGVv.2.3software(BroadInstitute).
Statisticalanalysis
SPSSStatisticsforWindowsv.21.0(IBMCorp.---Armonk,NY, United States) wasused for statistical analysis. Quantita-tivevariableswereanalyzed usingthechi-Squaredtestor Fisher’sexacttestwhereneeded,andqualitativevariables were analyzed using the Mann---Whitney U test. Corre-lation between qualitative variables was assessed using Spearman’scorrelationtest.Thestatisticallysignificant dif-ferencewaspredeterminedasp<0.05forallanalyses.
Table1 PCRprimerpairs,locus-specificsequences,andsequencesaddedforPCRindex. Primers CYP2J2-50F TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCTCCTAGCCTGGCCTTTTCTGAGAC CYP2J2-50R GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAGCATGGCTCAGACGTCCTCCTGCTC Locus-specificsequences CYP2J2-50F CTCCTAGCCTGGCCTTTTCTGAGAC CYP2J2 -50R CATGGCTCAGACGTCCTCCTGCTC
SequencesaddedforindexPCR
seq(i5)+adapter Inconstructedprimer TCGTCGGCAGCGTCAGATGTGTATAAGAGACAG seq(i7)+adapterinconstructedprimer GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAG
Results
Patientcharacteristicsandclinicalfeaturesof psoriasis
Patientcharacteristicsandclinicalfeaturesofpsoriasisare summarizedintable2.Forty-sevenpercentofthepatients weremaleand53%werefemale.Themeanageofpatients was44.66(SD=12.6)andmeanageofpsoriasisdiagnosiswas 33.21(SD=14.9).Theageofpatientsandageofdiagnosis weresimilarinbothmaleandfemalepatients(p=0.39and 0.53,respectively).
The mean PASI of psoriasis patients was calculated as 4.51 (SD=3.86). Psoriasis vulgaris was the most common typeof psoriasisand wasidentifiedin 76%of all psoriasis patients.Palmoplantarpsoriasiswasthesecondmost com-montype ofpsoriasis (11%),followed by guttate psoriasis (6%), erythrodermic psoriasis (4%), and pustular psoriasis (3%). Involvementof at least one ofthe special locations suchasthescalp,flexuralregion,orgenitalregionwas iden-tifiedin74.5%ofpsoriasispatients.Scalpinvolvementwas most frequently affected special location. Arthralgia was identifiedin 47% ofpsoriasis patients and23% ofpatients werediagnosedwithpsoriaticarthritis.
Previous and treatment treatments are summarized in
table 2.Topical steroids werethe most commonprevious
andcurrent treatment ofpsoriasispatients (99%and 90%, respectively).Among thepatients,23.1% hadatleast one associatedsystemicdiseaseorcomorbidity.Cardiovascular diseases were present in 11.7% of the patients and other systemicdiseaseswerepresentin22.2%(Table2).
CYP2J2genepolymorphismanalysis
AllelefrequencyandgenotypedistributionofCYP2J2gene inpsoriasispatientsandcontrolsaresummarizedintable3. TalleleandTT+GTgenotypeinthedominantmodelwere morefrequentinpsoriasispatientscomparedtocontrols(T allelefrequency 9.04%vs.4.5% andTT+GTgenotype fre-quency17.02% vs. 8%) butthis clinical differencedid not reachastatisticallysignificantlevel(p=0.063andp=0.062, respectively).Psoriasispatientsweredividedintotwo sub-groups as psoriasis vulgaris (PsV) and non-vulgar psoriasis (nVP). Subgroup analysis showed that both T allele and TT+GTgenotypefrequencieswereincreasedinPsVpatients comparedtocontrolgroup(p=0.024andp=0.029, respec-tively),indicatingthatCYP2J2polymorphismwasassociated
Table 2 Patient characteristics and clinical features of psoriasis. Characteristic n(%) Age(years) 45(36---54)a Sexmen, 45(47.9) Clinicaltype Psoriasisvulgaris 71(75.5) Non-vulgarpsoriasis 23(24.5) Ageofpsoriasisdiagnosis 31(21---46)a
PASI 4.2(1.85---6.9)a
Presenceofinvolvementofspeciallocations
Scalp 57(60.6) Nail 31(33) Flexuralregion 24(25.5) Genitalregion 21(22.3) Presenceofarthralgia 46(48.9) Presenceofarthritis 23(24.5) Positivefamilyhistoryforpsoriasis 26(7.7)
Previoustreatments Topicalsteroids 93(98.9) Systemictreatments 52(55.3) Phototherapy 3(3.2) Biologics 2(2.1) Currenttreatments Topicalsteroids 85(90.4) Systemictreatments 39(41.5) Phototherapy 12(12.8) Biologics 21(22.3)
Associatedinternaldiseasesandcomorbidities
Cardiovasculardiseases 11(11.7) Othersystemicdiseases 22(22.2) a Datapresentedasmedian(IQR).
PASI,PsoriasisAreaandSeverityIndex.
withincreased risk of developing PsV (OR=2.82, 95% CI: 1.11---7.15,p=0.029).
Demographicfeaturesanddiseasecharacteristicsof pso-riasis patients with GG genotype (wild type) and GT+TT genotype(homozygousorheterozygouspolymorphism)were comparedandsummarizedintable4.Althoughpatientswith PsVaremorefrequentthanpatientswithnPVinpolymorphic group (>2-fold), the result wasn’t statistically significant (p=0.22).Ageandsexof thepatients,ageof onset,PASI,
Table3 AllelefrequencyandgenotypedistributionofCYP2J2geneinpsoriasispatientsandcontrols. Psoriasis(all forms) (n=94) n(%) PsV(n=71) n(%) Control (n=100) n(%) p-value (psoriasis [allforms] vs.control) p-value (PsVvs. control) OR(95%CI) (psoriasis [allforms] vs.control) OR(95%CI) (PsVvs. control) Genotype Dominant model TT+GT 16(17.02) 14(19.8) 8(8) 0.062 0.029 2.35(0.96---5.8) 2.82(1.11---7.15) GG 78(82.97) 57(80.2) 92(92) Recessive model TT 1(1.06) 1(1.4) 1(1) 0.96 0.807 1.07(0.07---17.3) 1.41(0.09---22.9) GT+GG 93(98.94) 70(98.6) 99(99) Allele G 171(90.96) 127(89.5) 191(91.2) 0.063 0.024 T 17(9.04) 15(10.5) 9(4.5) PsV,psoriasisvulgaris.
Table4 DemographicfeaturesanddiseasecharacteristicsofpsoriasispatientswithGGgenotypeandGT+TTgenotype. CYP2J2 GG CYP2J2 GT+TT p-Value Psoriasistype(PsV/nVP) 57/21 14/2 0.22 Age 44.6(10.9) 46(15.9) 0.90 Ageofonset 30(13.7) 31(16.1) 0.41 PASI 4.5(4) 5.2(2.8) 0.81 Sex,male/female 27/29 7/8 0.92
Presenceofinvolvementofspeciallocations
Scalp 66.1 73.3 0.59 Nail 37.5 26.7 0.44 Flexuralregion 26.8 26.7 0.99 Genitalregion 25 13.3 0.34 Presenceofarthralgia 50 53.3 0.82 Presenceofarthritis 21.4 26.7 0.67
Positivefamilyhistoryforpsoriasis 35.7 20 0.25
Presenceassociatedinternaldiseasesandcomorbidities 26.8 20 0.59
presenceof involvement ofspecial locations,presence of arthralgiaand arthritis,positive familyhistory for psoria-sis,presence associated internal diseases, and treatment modalitiesweresimilarbetweenpsoriasispatientswithand withoutpolymorphism.
Discussion
This study investigated the possible role of CYP2J2 poly-morphismasariskfactorinpsoriasispatients.Theresults demonstrateasignificantlyhigherfrequencyof Tallelein psoriasisvulgaris patientsand anincreased riskof psoria-sisin patientswithCYP2J2polymorphisminthedominant model. To the best of the authors knowledge, this is the firststudyinvestigatingtheroleofCYP2J2polymorphismin psoriasis.
CYP2J2 50G>T is one of the most studied functional CYP2J2polymorphisms.Spiecker etal. studied the effect of CYP2J2 50G>T polymorphism and observed a decrease inbinding oftranscription factor Sp1 toDNA,areduction inpromoteractivity,andlowerEETplasmaconcentrations in patientswith G-50Tpolymorphism compared withwild
typeparticipants.19CYP2J2-derivedEETsinduce
vasodilata-tion;inhibitinflammation, apoptosis,andthrombosis;and show cardio-protectiveeffects.20 By altering their plasma
concentrations, CYP polymorphism mayaffect the cardio-protectiveroleofEETsandplayaroleinthepathogenesis ofcardiovasculardiseases.
CYP2J2polymorphism has been studied mainly in car-diovascular diseases, with contradictory results among differentethnicgroups. StudiesinvestigatingCYP2J2 poly-morphismincoronaryarterydiseasesrevealedan increase risk in the German population, decreased risk in African Americans,andnoassociationinCaucasiansandtheSwedish population.18,19,21,22 Polonikov et al. showed an increased
risk of hypertension in Russian patients; however, this association couldn’t be confirmed in African Americans or Caucasians.23---25 Polonikov et al. also described a
sex-specific relationship between CYP2J2 polymorphism and hypertension in female Russian patients.26 No significant
association betweenCYP2J2polymorphismandstrokewas identified in Swedishand Chinesepopulations.18,27 Recent
studies also demonstrated that CYP2J2 increased circu-lating EET levels, induced angiogenesis, and improved cardiac function in rats after myocardial infarction.28
Cardiovasculardiseasesarefrequentandimportant comor-bidities in psoriasis. The present study evaluated the association between CYP2J2 polymorphismand cardiovas-cularcomorbidities.Nosignificantassociationwasobserved betweenCYP2J2polymorphismandcomorbidityfrequency, suggesting that CYP2J2 mayincrease the risk of develop-ingpsoriasisvulgaris,but thatitis notassociatedwithan increased risk of cardiovascular comorbidities in psoriasis patients.
Besides itscardiovascular effects,CYP2J2-derived EETs also modulate inflammation.29 Node et al. studied the
effect of CYP2J2-derived EETs on vascular inflammation. TheirstudyrevealedthatEETsmaymodulateinflammatory responsebyinhibitionofpro-inflammatorycytokine-induced (TNF-␣, IL-1␣, and bacterial lipopolysaccharide) expres-sion of vascular endothelial adhesion molecules (VCAM-1, ICAM-1, and E-selectin) and decrease the number of rolling/adherentmononuclearleucocytes.29 EETsalsoshow
theiranti-inflammatoryeffectsthroughinhibitionofnuclear factor-kappaB (NF-B) and IB kinase, activation of peroxisome proliferator-activated receptors, increase of eNOSexpression, andregulationofendoplasmicreticulum homeostasis.30
Although the anti-inflammatory effect of EETs is well documented, there are only a few studies investigating CYP2J2polymorphismininflammatorydiseases.Wangetal. studiedCYP2J2polymorphismindiabetesmellituspatients. Although nosignificant difference was observed between diabetic patients and a control group; among diabetic patients,CYP2J2polymorphismwasshowntobeassociated withyounger age of onset.31 The present authorsstudied
CYP2J2polymorphism inpsoriasis,a chronicinflammatory skindisease,andrevealedanincreasedriskofpsoriasisin patients withCYP2J2 polymorphism. In the pooled analy-siswhereallpsoriasispatientswereincluded,althoughCYP polymorphism washigher inpsoriasis patients,the results didnotreachstatisticalsignificance.Inthesubgroup analy-sisofpsoriasissubtypes,astatisticallysignificantdifference between CYP polymorphism of psoriasis vulgaris patients and the control group was observed. CYP polymorphism wasidentifiedasariskfactor forPV butnotfornVP. Pso-riasis is an inflammatory skin disorder in which genetic susceptibility has a significant effect on pathogenesis of thedisease.Familyhistory ofpsoriasisdiffers among eth-nicgroups andthe prevalenceof apositive familyhistory isestimatedatapproximately30%.32,33 PSORS1andPSORS2
aretwoofthebestknownsusceptibilitylocifor psoriasis. HLA-C*06:02 is located at the PSORS1 locus and the role of HLA-C*06:02 in psoriasis is well known. Recent studies confirmed the importance of HLA-C*06:02 in genetic sus-ceptibility of psoriasis along with itseffect ontreatment responses.34 Together with HLA-C*06:02, a large genetic
study conductedbyZhou etal.revealed severalnew sus-ceptibility loci,such as HLA-C*07:04,rs118179173, HLA-B amino acid 67, HLA-DPB1*05:01, and BTNL2 amino acid 281.35 Caspase recruitment family member 14 (CARD14)
is located at PSORS2 locus and activatesthe NF-B path-way.CARD14hasbeenclassifiedasapsoriasissusceptibility geneandmanyrecentstudieshavefocusedon demonstrat-ing the role of CARD14 in the pathogenesis of psoriasis. Gain-of-function mutations of CARD14 activate the NF-B signal transductionpathway, and increasedNF-Bactivity
dueto CARD14mutations is shown tobe linkedto pustu-larpsoriasis.36Zhuetal.alsoinvestigatedCARD14variants
inpatientswithpsoriasisvulgaris.The studyrevealedfive mutations,butthemutationswerealsoseeninthecontrol groupanda clearmutation-disease relationship couldnot bedefined.37 Tanakaetal.investigatedtheimmunological
roleofCARD14inpsoriasismurinemodelandshowedthat IL23mRNA expression and IL-17 producing T cell infiltra-tionwasdecreased inCARD14-deficient mice.38 The study
also showed that psoriasiform inflammatory skin changes weredecreased in CARD14-deficient mice, suggesting the possibleimmune inflammatoryroleof CARD14 inpsoriasis pathogenesis.38 Besides PSORS1 and PSORS2, many
psori-asis susceptibility loci were identified with genome-wide association studies (GWAS).Tsoiet al.performed aGWAS meta-analysisandidentified16newsusceptibilitylocithat regulate the I-B kinase/NF-B pathway and cytotoxic-ity, and that respond to external stimuli and leukocyte differentiation.39 In addition to these genetic variations
somesubtype specific mutationsand polymorphismswere alsoidentified.Lietal. showedthatpolymorphism inthe IL-36 receptor antagonist gene (IL36RN) was associated withincreased risk of pustular psoriasis.40 Twelves et al.
investigatedtheIL36RNmutationfrequenciesbetween dif-ferentpustularpsoriasissubtypesandrevealedthatIL36RN mutationsweremorefrequentamongpatientswith gener-alizedpustularpsoriasis.41Studiesshowingdifferentgenetic
backgroundindifferentpsoriasissubtypessuggestthat non-vulgar psoriasis maybe a different disease rather than a subtypeof psoriasis, which is consistent withthe present results.
TheresultsshowednoassociationbetweenCYP2J2 poly-morphism and clinical characteristics of psoriasis. The psoriasispatientsincluded inthestudyweremostlyunder treatment; with treatment, major clinical characteristics suchasPASI,nailinvolvement,arthralgia,andarthritiscould bemodified.
Oneofthelimitationsofthisstudyisthatitdidnotstudy theEET concentrations and theirassociation withCYP2J2 polymorphism. CYP2J2 polymorphism may contribute to inflammatoryprocessandpathogenesisofpsoriasisthrough alteringETTconcentrations,buttounderstandthe psoriasis-CYPpolymorphism-ETTrelationship better,furtherstudies are needed. Another limitation is the limited number of psoriasis patients with cardiovascular comorbidities. We didnotshowany relationship betweenCYP polymorphism andcomorbidities,but thiscouldbedue totypeII (beta) error.
The genetic basis of psoriasis is complex and differs amongethnicgroupsaswellaspsoriasissubtypes.CPY poly-morphism --- like other polymorphisms --- may vary among ethnicgroups.In ordertogeneralizetheseresultsfurther studies of different ethnic groups and different psoriasis subtypesareneeded.
Financial
support
Thisstudywassupportedbyaresearchgrantfromthe Turk-ishSocietyofDermatology(2017/53).
Authors’
contribution
YıldızHayran:Statisticalanalysis;approvalofthefinal ver-sion of the manuscript; conception and planning of the study;compositionofthemanuscript;collection, analysis, andinterpretationofdata;participationinthedesignofthe study;intellectualparticipationinthepropaedeuticand/for therapeuticconductofthestudiedcases;criticalreviewof theliterature;criticalreviewofthemanuscript.
Nuran Allı: Approval of the final version of the manuscript;criticalreviewofthemanuscript.
Pınar ˙IncelUysal:Compositionofthemanuscript; collec-tion,analysis,andinterpretationofdata.
Tuba C¸andar:Participation in the design of the study; criticalreviewofthemanuscript.
Conflicts
of
interest
Nonedeclared.
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