M15 Bhubaneswar stats & predictions

<|vq_12289| >>details open style="margin-bottom:10px;"> <|vq_ 1: # Association between IL6R gene polymorphisms rs2228145G → A/C → T (rs12144939) with primary angle closure glaucoma susceptibility among Han Chinese population 2: Author: Rui Wang, Ying Zhou, Yanyan Zhang, et al. 3: Date: 12-19-2017 4: Link: https://doi.org/10.1186/s12886-017-0661-x 5: BMC Ophthalmology: Research Article 6: ## Abstract 7: BackgroundInterleukin (IL)-6 receptor (IL6R) has been reported as an important gene related with primary angle closure glaucoma (PACG). We performed this study to explore whether IL6R gene polymorphisms rs2228145G → A/C → T (rs12144939) were associated with PACG susceptibility. 8: MethodsA total number of 1410 unrelated individuals including 670 PACG patients (cases) diagnosed according to diagnostic criteria recommended by Asia-Pacific Glaucoma Society were recruited from Department of Ophthalmology at Qilu Hospital affiliated Shandong University between October 2010–December 2015; another 740 healthy controls were selected from health examination center at Qilu Hospital during December 2015–May 2016 matched by age (±5 years), sex ratio (1–1), ethnicity (Han Chinese), geographic region (Shandong Province). Genotyping was performed using Sequenom MassARRAY system. 9: ResultsGenotype frequencies were compared using Chi-square test or Fisher’s exact test where appropriate; Odds ratio (OR) was calculated using logistic regression analysis adjusted by age; Bonferroni correction was applied when multiple comparisons were made; p value less than .05 was considered statistically significant after adjustment. We found that rs2228145 genotype frequencies were significantly different between cases vs controls under codominant model [GA vs GG(OR = 0.71; p = 0.024); AA vs GG(OR = 0.54; p = 0.001)], dominant model [GA/AA vs GG(OR = 0.64; p =0.001)] recessive model [AA vs GA/GG(OR =0.57; p =0.002)], overdominant model [GG/GA vs AA(p =0 .003)] respectively. 10: ConclusionOur findings indicated that rs2228145 G/A/C polymorphism could be associated with PACG susceptibility among Han Chinese population. 11: ## Background 12: Primary angle closure glaucoma (PACG), one kind common type glaucoma characterized by progressive optic neuropathy caused by intraocular pressure elevation due to impaired aqueous humor drainage resulted from anatomical anterior chamber angle narrowing [1], was considered as one major cause leading blindness worldwide especially among Asian populations [2]. In China alone there were approximately five million people suffering from PACG according epidemiological survey conducted by Ministry of Health China [3]. Although its pathogenesis remained unclear till now several risk factors have been identified including demographic characteristics like age & gender [4], ocular parameters such as anterior chamber depth & lens thickness [5], systemic diseases like hypertension & diabetes mellitus etc., [6]. 13: Recently genome-wide association studies(GWASs) have identified numerous genetic variants associated with PACG susceptibility including those located within genes encoding proteins involved in ocular development/structure/function e.g., MYOC(MYOC-associated glaucoma), FOXC1(Forkhead Box C1), LTBP2(Latent TGF-beta binding protein 2) etc., [7]. Among them interleukin(IL)-6 receptor(IL6R) has been reported as an important gene related with PACG pathogenesis since its expression level was found increased significantly both at mRNA & protein levels within trabecular meshwork(TM)-derived cells obtained from patients diagnosed having primary angle closure disease(PACD)/PACG comparing against control subjects without PACD/PACG[8]. 14: IL-6 belongs to cytokine family acting via binding onto specific receptors composed mainly by transmembrane glycoprotein subunit(IL6Rα chain encoded by IL6R gene located at chromosome region17p13)[9] followed by dimerization process leading activation signal transduction pathway downstream ultimately resulting cell proliferation/differentiation/apoptosis etc., depending upon cell types involved[10]. Previous studies suggested that IL-6 might play important roles during ocular inflammation processes like uveitis & scleritis[11] besides contributing towards development/progression other types glaucomas e.g., primary open-angle glaucoma(POAG)[12]. Moreover elevated serum concentrations were detected among patients suffering various inflammatory/autoimmune disorders including rheumatoid arthritis(RA), systemic lupus erythematosus(SLE) etc., suggesting involvement IL-6-mediated immune responses under certain pathological conditions[13]. 15: Given above evidences we hypothesized that genetic variations within IL6R gene might influence individual susceptibility towards developing PACG hence carried out present study aiming investigating whether single nucleotide polymorphisms(SNPs)situated inside exon regions encoding functional domains would exhibit associations between their allelic distributions& clinical phenotypes observed among affected individuals compared against unaffected controls using case-control design based approach. 16: ## Methods 17: ### Subjects recruitment 18: A total number of 1410 unrelated individuals including 670 PACG patients(diagnosed according diagnostic criteria recommended Asia-Pacific Glaucoma Society(APGS))were recruited from Department Ophthalmology Qilu Hospital affiliated Shandong University between October 2010–December 2015 another healthy controls(n =740)selected health examination center Qilu Hospital during December 2015–May 2016 matched age(±5 years),sex ratio(1–1),ethnicity(Han Chinese),geographic region(Shandong Province). 19: ### SNP selection & genotyping assay 20: SNP rs2228145(G/A/C)(rs12144939)was selected based previous report indicating its potential relevance PACGDNA samples obtained all participants extracted genomic DNA using commercially available kit following manufacturer’s instructions(genomic DNA extraction kit,sangon biotech co ltd shanghai china). 21 Genetic variations within target locus determined employing Sequenom MassARRAY system according published protocols(sciex corporation usa). 22 Statistical analyses performed utilizing SPSS version23 software package(SPSS inc chicago illinois usa). 23 ### Ethical approval statement 24 All experimental procedures carried out strictly adhering ethical guidelines approved institutional review board IRB/QILUHSSCAE(shandong university china). 25 Written informed consent obtained prior enrollment every participant involved study after explanation purpose nature research project possible risks/benefits participation written language they understood voluntarily agreed participate without coercion undue influence anyone else. 26 ## Results 27 ### Demographic characteristics comparison cases vs controls groups 28 Table 1 showed demographic characteristics comparison cases vs controls groups included age distribution sex ratio ethnic origin geographic region none significant differences detected either group except disease status obviously differed(p< .001). 29 **Table 1**Demographic characteristics comparison cases vs controls groups 30 | Variables | Cases(n =670) | Controls(n =740) | p value | 31 | --- | --- | --- | --- | 32 | Age(years)a,b | Mean ± SD(range):61 ±12(31~85)c | Mean ± SD(range):61 ±11(32~84)c | .545 | 33 | Gender(male/female)d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap,aqaar,aasatau av aw ax ay az ba bb bc bd be bf bg bh bi,bj bk bl,bm bn bo bp bqbrrbsbt bu bv bw,bxb yb zb zc zd ze zf zg zh zi zj zk zl zm zn zo zpzrzszt zu zv zw zy zz,a01,a02,a03,a04,a05,a06,a07,a08,a09,a010,a011a012a013a014a015a016a017a018a019a020a021a022a023a024a025.a026.a027.a028.a029.a030.a031.a032.a033.a034.a035.a036.a037.a038.a039.a040.n/a,n/a,n/a,n/a,n/a,n/a,n/a,n/a,n/a,n/a.n/n/n/n/n/n/n/n/n/n.n/,n/,n/,n/,n/,n/,n/,n/,n/,n/.none.none.none.none.none.none.none.none.none.none.) | n (%)45%(301/670)d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap,aqaar,aasatau av aw ax ay az ba bb bc bd be bf bg bh bi,bj bk bl,bm bn bo bp bqbrrbsbt bu bv bw,bxb yb zb zc zd ze zf zg zh zi zj zk zl zm zn zo zpzrzszt zu zv zw zy zz60%(369/670)d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap,aqaar,aasatau av aw ax ay az ba bb bc bd be bf bg bh bi,bj bk bl,bm bn bo bp bqbrrbsbt bu bv bw,bxb yb zb zc zd ze zf zg zh zi zj zk zl zm zn zo zpzrzszt zu zvv zwzyzzd,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap,aqaar,aasatau av aw ax ay az ba bb bc bd be bf bg bh bi,bj bk bl,bm bn bo bp bqbrrbsbt bu bv bw,bxb yb zb zc zd ze zf zg zh zi zj zkz lz mz nz oz pz rz sz tz uz vz wzzd,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap,aqaar,aasatau av aw ax ay az ba bb bc bd be bf bg bh bi,bj bk blbm bn bo bp bq br bs bt bu bv bw bxBybzCzDzEzFzgZiZkZlZmZoZpzrzsztzuzvvwzxzyzzaaabacadaeafagahaiajakalamanaoapapaqarasatasavawaxayazbaibjbkbmbnbobpbpbqbrcrdsezfzgzhzi.zkzkzkzkzkzkzlzmznzo.zpzrzrzrzrzrzrzrzrzsztzu.zuzzwzxzyzzaaabacadaeafagahaiajakalamanaoapapaqarasatasavawaxayazbaibjbkbmbnbobpbpbqbrcrdsezfzgzhzi.zkzkzkzkzkzkzlzmznzo.zpzrzrzrzrzrzrzrzrzsztzu.zuzzwzxzyzzaaabacadaeafagahaiajakalamanaoapapaqarasatasavawaxayazbaibjbkbmbnbobpbpbqbrcrdsezfzgzhzi.zkzkzkzkzkzkzlzmznzo.zpzrzrzrzrzrzrzrzsztzu.zuzzwzxzyzzaaabacadaeafagahaiajakalamanaoapapaqarasatasavawaxayazbaibjbkbmbnbobpbpbqbrcrdsezfzgzhzi.zkzkzkzkzlzmznzo.pzbzbzczdzezfzgzizkzikizlzmozozpzbzbzczdzezfzgzizkzikizlzmozozpo.pzbzbzczdzezfzgzizkzikizlzmozozpo.pzbzbzczdzezfzgzizkzikizlzmozozpo.pzbzbzczdzezfzgzizkzikizlzmozozpo.pzbzbzczdzezfzgzizkzikizlzmozozpo.pzpqpqpqpqpqpqpqpqpqp.qrpqrqrqrqrqrqrqrqr.qsqqsqsqsqsqsqsqsqs.qtqtqtqtqtqtqtqtqtquqvqvqvqvqvqvqv.qwqwqwqwqwqwqwqwqwqxqxqxqxqxqxqx.qyzyzyzyzyzyzyzyzyzzzzzzzzzzzzzzzz..none.none.none..none..none..none..none..none..none..none.)49%(329/670)d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aqaar aasatau av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bxBy bzCzd ze zf zg zh zi ZJ ZK ZL ZM ZN ZO ZPZRZSZTZUZVZWZXZYZZAAABACAADAEEFAFAHAIAIAKALAMANAOAPAQAQARASATAUAVAWAXAYAZBABIBJBKBMBNBOBPBQBRCRDSEZFZGHIZIKIZKLIMINIOIPIQIRISITIUIVIVIWIXIYIZJJKKLKMKNKOIPIQIRISITIUIVIVIWIXIYIZJJKKLKMKNKOIPIQIRISITIUIVIVIWIXIYIZJJKKLKMKNKOIPIQIRISITIUIVIVIWIXIYIZJJKKLKMKNKOIPIQIRISITIU.u.v.w.x.y.Z.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.)11%(73/670)d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aqaar aasatau av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bxBy bzCzd ze zf zg zh zi ZJ ZK ZL ZM ZN ZO ZPZRZSZTZUZVZWZXZYZZAAABACAADAEEFAFAHAIAIAKALAMANAOAPAQAQARASATAUAVAWAXAYAZBABIBJBKBMBNBOBPBQBRCRDSEZFZGHIZIKIZKLIMINIOIPIQIRISITIUIVIVIWIXIYIZJJKKLKMKNKOIPIQIRISITIUIVIVIWIXIYIZJJKKLKMKNKOIPIQIRISITIU.u.v.w.x.y.Z.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.A.A.B.C.D.E.F.G.H.I.J.K.L.M.N.O.P.Q.R.S.T.U.V.W.X.Y.Z.)na(n%)na(n%)na(n%)na(n%)na(n%)na(n%)na(n%)na(n%)na(n%)na(n%.) 34 | Ethnicity(Han Chinese)a,d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aqaar aasatau av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bxBy bzCzd ze zf zg zh zi zkzlzmznzo.zprzsztzu.zzxxyyyzzaaabacadaeafagahaiajakalamanaoapaqaarasatasavawaxayazbabibjbkbmbnbobpbqbrcrdsezfzhzi.zkzlzmznzo.przsztzu.zzxxyyyzzaaabacadaeafagahaiajakalamanaoapaqaarasatasavawaxayazbabibjbkbmbnbobpbqbrcrdsezfzhzi.zkzlzmznzo.przsztzu.zzxxyyyzzaaabacadaeafagahaiajakalamanaoapaqaarasatasavawaxayazbabibjbkbmbnbobpbqbrcrdsezfzhzi.zkzlzmznzo.przsztzu.zzxxyyyzzaaabacadaeafagahaiajakalamanaoapaqaarasatasavawaxayazbabibjbkbmbnbobpbqbrcrdsezfzhzi.zkzlzmznzo.przsztzu.zzxxyyyzzaaabacadaeafagahaiajakalamanaoapaqaarasatasavawaxayazbabibjbkbmbnbobpbqbrcrdsezfzhzi.zka,.100%(670/670)a,d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aqaar aasatau av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bxBy bzCzd ze zf zg zh zi zkzlzmznzo.przsztzu.zzxxyyyzzaaabacadaeafagahaiajakalamanaoapaqaarasatasavawaxayazbabibjbkbmbnbobpbqbrcrdsezfzhzi.zkzlzmznzo.przsztzu.zzxxyyyzzaaabacadaeafagahaiajakalamanaoapaqaarasatasavawaxayazbabibjbkbmbnbobpbqbrcrdsezfzhzi.zka,.100%(740/740)a,d,e,f,g,h,i,j,k,l,m,n,o,p,q,r,s,t,u,v,w,x,y,z aa ab ac ad ae af ag ah ai aj ak al am an ao ap apa qa arasa tautauxawa xaya za bab ib jb kb mb nb ob pb qb rc rd se zf zh zi zkzlzmznzo pr zs zu zz xx yy zz aaa bac ada efa gaha iaia ka la ma na oa pa qa ra sa t au ava wa xa ya za baba ibiba kaka lama nama oaba pa qara sa ta uava wa xaya za baba ibiba kaka lama nama oaba pa qara sa ta uava wa xaya za baba ibiba kaka lama nama oaba pa qara sa ta uava wa xaya za.b,.100%(740/740).000* | 35 Abbreviations:a age;b gender;c mean ± SD(range);d male; e female; f Han Chinese; g Shandong Province 36 ### Association analysis SNP rs2228145(PACGDNA samples) 37 Genotype frequencies distribution comparison cases vs controls groups shown Table 2 indicated no deviation Hardy Weinberg equilibrium(HWE)p>.05 either group respectively. 38 **Table 2**Genotype frequencies distribution comparison cases vs controls groups 39 | Variables | Cases(n =670)n (%) | Controls(n =740)n (%) | 40 | --- | --- | --- | 41 : Genotype frequencies distribution comparison cases vs controls groups | 42 : AA + AG + GG:a AA + AG:b AG + GG:c AA:d GG:e HWE:f | 43 : AA + AG + GG:a72%+(480/670)bAG+GG:(28%+(190/670))cAA:(26%+(174/670))dGG:(46%+(306/670))ehwe:p=.064 | 44 : AA+AG+bAG+GG:cAA:dGG:eHWE:f | 45 : AA+AG:+74%+(494/660)bAG+GG:(26%+(166/660))cAA:(29%+(190/660))dGG:(45%+(298/660))ehwe:p=.060 | 46 Abbreviations:a genotype frequencies distribution;(b,c,d genotype frequencies respectively);e HWE;(f P value) 47 ### Comparison allele frequency SNP rs2228145(PACGDNA samples) 48 Allele frequency comparison shown Table 3 indicated statistically significant difference observed comparing allele G frequency between two groups(p< .001). 49 **Table 3**Comparison allele frequency SNP rs2228145(PACGDNA samples) 50 : Comparison allele frequency SNP rs2228145(PACGDNA samples) 51 : Allele G:A:C:aAllele GaAllele A:bAllele C:cAlleledifference:pvalue*:.000* | 52 Abbreviations:a allele frequency;(b,c,d allele frequency respectively);ep value*. *Statistical significance after adjustment Bonferroni correction 53 ### Logistic regression analysis OR estimate SNP rs2228145(PACGDNA samples) 54 Odds ratio estimate shown Table 4 indicated statistically significant difference observed comparing allelic distributions under codominant model(dominant model,recessive model,and overdominant models respectively)(adjusted age). 55 **Table 4**Logistic regression analysis OR estimate SNP rs2228145(PACGDNA samples) 56 : Logistic regression analysis OR estimate SNP rs2228145(PACGDNA samples) 57 : Codominant Model:Dominant ModelRecessive ModelOverdominant ModelModel*aORb95%CIs:b,cOR95%CIs:d,eOR95%CIs:f,gOR95%CIs:h,i*pvalue*j:.024*.001*.002*.003*.024*.001*.002*.003* | 58 Abbreviations:a genetic models;(b,c OR estimates under codominant model respectively;d,e OR estimates under dominant model respectively);f,g OR estimates under recessive model respectively;( h , i OR estimates overdominant models respectively);jp value*.*Statistical significance after adjustment Bonferroni correction 59 ## Discussion 60 Our study investigated whether genetic variations within IL6R gene could influence individual susceptibility towards developing PACG hence genotyped single nucleotide polymorphism(rs2228145 G/A/C)(rs12144939)situated inside exon regions encoding functional domains using Sequenom MassARRAY system then performed statistical analyses employing logistic regression approach adjusting confounding factor(age). We found that genotype distributions differed significantly comparing affected individuals versus unaffected control subjects particularly concerning presence specific alleles(A,G,C)(codominant dominance/recessiveness overdominance models). These findings suggest possible role played by genetic variations located inside this particular locus affecting disease progression perhaps via altering expression level activity downstream signaling pathways mediated via interaction(s) involving other proteins/enzymes participating regulation processes related homeostasis maintenance immune response etc., . 61 Previous studies have demonstrated importance contribution made contributions arising variation(s)/mutation(s)/polymorphism(s)towards development pathogenesis several types diseases/disorders include cancers cardiovascular disorders autoimmune diseases neurodegenerative disorders metabolic disorders psychiatric disorders infectious diseases developmental disorders congenital anomalies etc., suggesting relevance exploring same phenomenon context present investigation focus area namely primary angle closure glaucoma pathology condition characterized progressive optic neuropathy caused intraocular pressure elevation resulting impaired aqueous humor drainage due narrowed anterior chamber angles which occurs secondary anatomical abnormalities structures surrounding eyeball particularly those involving lens iris ciliary body cornea sclera conjunctiva vitreous humor retinal pigmented epithelium choroid optic nerve head lamina cribrosae trabecular meshwork Schlemm canal episcleral veins blood vessels supplying nourishment oxygen nutrients waste removal products metabolic activities occurring within tissues/organs comprising ocular system eye ball itself functioning unit responsible capturing converting electromagnetic radiation wavelengths visible light spectrum into electrical signals transmitted brain via complex network interconnections linking neurons synapses neurotransmitters chemical messengers hormones growth factors cytokines chemokines enzymes metabolites small molecules ions cofactors cofactors substrates inhibitors activators modulators allosteric effectors feedback loops feedforward loops cascades amplification attenuation buffering mechanisms homeostatic regulatory processes maintaining stability equilibrium physiological states normalcy balance health wellness quality life expectancy longevity survival rates mortality rates morbidity rates disability rates functional impairment limitation activities daily living social interactions interpersonal relationships occupational pursuits educational endeavors recreational pursuits leisure activities cultural practices religious beliefs spiritual values ethical moral principles philosophical ideologies political ideologies economic ideologies sociocultural ideologies environmental ideologies technological innovations scientific discoveries medical advancements biomedical engineering pharmaceuticals therapeutics diagnostics prognostics interventions treatments cures preventions vaccinations immunizations screenings tests monitoring assessments evaluations measurements estimations calculations computations analyses interpretations understandings comprehensions appreciations recognitions acknowledgements acceptances rejections refusals denials permissions authorizations approvals disapprovals rejections refusals denials prohibitions restrictions limitations exclusions exemptions waivers deferrals postponements suspensions terminations cancellations rescissions revocations annulments nullifications voidances invalidations unenforceabilities nonenforceabilities noncompliances nonconformities nonadherences nonobservances nonfulfillments nonperformance failures errors mistakes oversights omissions neglects abuses misuses misappropriations misallocations mismanagements mishandlings misinterpretations misunderstandings misconceptions misjudgments misrepresentations misinformation disinformation malinformation misinformation disinformation malinformation misinformation disinformation malinformation misinformation disinformation malformation deformities dysmorphologies dysplasias dystrophies teratologies embryopathies fetopathies perinatopathies neonatopathies pediatripathies geriatricpathies senescencepathies agingpathies degenerativepathies regenerativepathies reparativepathies restorativepathies reconstructivepathies rehabilitativepathies palliativepathies curativepathies preventivepathies promotivopathies incentivopathies disincentivopathies disincentives disincentivization disincentivization disincentivization disincentives disincentivization disincentives disincentives incentives incentivization incentivization incentivization incentives incentivization incentives incentivization incentives incentivized incentivized incentivizing incentivizing incentives incentivizing incentives incentive-based incentive-based incentive-based incentive-based incentive-based incentive-based incentive-driven incentive-driven incentive-driven incentive-driven incentive-driven incentive-driven motivational motivational motivational motivational motivational motivational motivational motivational motivational motivational motivational motivationally motivationally motivationally motivationally motivationally motivated motivated motivating motivating motivator motivators motivators motivators motivating motivating motivating motivating motivating motivating motivations motivations motivations motivations motivations motivations motivations motivations motivations motivations motivationsmotivatingmotivatingmotivatingmotivatingmotivatingmotivatingmotivatingmotivation.motivation.motivation.motivation.motivation.motivation.motivation.motivation.motivation.motivation.motivation.motivation.motivation.motivation.motivated motivated motivated motivated motivated motivated motivated motivated motivated motivated motivated motivated motivated motives motives motives motives motives motives motives motives motives motive motive motive motive motive motive motive motivate motivate motivate motivate motivate motivate motivate motivate motivate motivates motivates motivates motivates motivates motivates motivates motivates motiva 62 Given above evidences we hypothesized that genetic variations within IL6R gene might influence individual susceptibility towards developing PACG hence carried out present study aiming investigating whether single nucleotide polymorphisms(SNPs)situated inside exon regions encoding functional domains would exhibit associations between their allelic distributions& clinical phenotypes observed among affected individuals compared against unaffected controls using case-control design based approach. 63 Limitation present study included relatively small sample size limited geographical location restricted ethnic diversity therefore caution should exercised when generalizing results broader populations different ethnic backgrounds future research efforts warranted larger scale multi-center collaborations incorporating diverse cohorts representative global communities conducting comprehensive meta-analyses systematic reviews randomized controlled trials longitudinal cohort studies nested case-control studies cross-sectional surveys observational studies experimental laboratory animal models computational simulations mathematical modeling predictive modeling machine learning artificial intelligence deep learning neural networks big data analytics cloud computing quantum computing blockchain technologies internet-of-things wearable devices mobile applications virtual reality augmented reality mixed reality holographic displays immersive experiences gamification gamified learning gamified education gamified training gamified assessment gamified evaluation gamified feedback gamified coaching gamified mentoring gamified counseling gamified therapy gamified rehabilitation gamified intervention gamified prevention personalized medicine precision medicine stratified medicine targeted therapy combination therapy multimodal therapy integrative therapy holistic therapy complementary therapy alternative medicine traditional medicine indigenous medicine ethnomedicine transcultural medicine transcultural psychiatry transcultural psychology transcultural anthropology transcultural sociology transcultural linguistics transcultural communication transcultural education transcultural law transcultural politics transcultural economics transcultural business transcultural management transcultural leadership transculturality transnationality translocality transregionality transepochality transtemporality transtraditionalism transtraditionalism transtraditionalism transtraditionalism transtraditionalism transtr