Cytokine Gene Associations Nrog Kev Tshaj Tawm Txog Tus Kheej Thaum sawv ntxov thiab yav tsaus ntuj qaug zog hauv cov neeg mob Oncology thiab lawv tsev neeg cov neeg saib xyuasⅠ

Abstract

Lub hom phiaj ntawm txoj kev tshawb fawb no yog los ntsuam xyuas qhov sib txawv ntawm cov kev hloov pauv hauv pro- thiabanti-mobcytokine genes ntawm cov neeg koom nrog uas tau muab cais raws li muaj qis thiab siabtheem ntawm kev qaug zog thaum sawv ntxov thiab yav tsaus ntuj thiab ntsuas qhov sib txawv ntawm cov yam ntxwv phenotypicntawm ob pawg no. Nyob rau hauv ib qho piv txwv ntawm 167 oncology outpatients nrog lub mis, prostate, ntsws, los yogmob qog nqaij hlav hlwb thiab 85 ntawm lawv tsev neeg cov neeg saib xyuas, kev loj hlob sib xyaw ua qauv (GMM) tau siv los uatxheeb xyuas cov chav kawm latent ntawm cov tib neeg raws li kev ntsuas thaum sawv ntxov thiab yav tsaus ntujqaug zogtauua ntej, thaum, thiab rau 4 lub hlis tom qab ua tiav kev kho hluav taws xob. Qhov sib txawv ntawm ib leegnucleotide polymorphisms (SNPs) thiab haplotypes hauv 15 cytokine noob tau soj ntsuam ntawmcov chav kawm latent. Ntau lub logistic regression tau siv los ntsuas cov txiaj ntsig ntawm phenotypic thiabgenotypic characteristics on morning and eveningqaug zogkev ua tswv cuab hauv chav kawm. Kev koom tes taupom thaum sawv ntxov qaug zog thiab tus naj npawb ntawm comorbidities nrog rau kev hloov pauv hauvTNFArs1800629 thiab rs3093662. Kev qaug zog yav tsaus ntuj tau cuam tshuam nrog kev saib xyuas menyuam yaus hauv tsev thiabvariations hauvIL 4rs2243248 ibTNFAib 2229094. Cov hnub nyoog yau thiab qis dua qhov ua tau zoo yogtxuam nrog rau thaum sawv ntxov thiab yav tsaus ntujqaug zog. Cov kev tshawb pom no qhia tiasmob Cov neeg kho kom haum xeeb yog txuam nrog kev loj hlob ntawm kev qaug zog thaum sawv ntxov thiab yav tsaus ntuj. Txawm li cas los xij, vimtxawv phenotypic yam ntxwv thiab genomic markers yog txuam nrog diurnal variations nyob rau hauvqaug zog, thaum sawv ntxov thiab yav tsaus ntuj qaug zog yuav txawv tab sis muaj feem xyuam nrog cov tsos mob.

Ntsiab lus

cytokines; noob caj noob ces; sawv ntxovqaug zog; yav tsaus ntujqaug zog; mob cancer ntawm lub mis; qog necrosis factor-alpha;interleukin 4;cistanche extract hmoov

anti-fatigue function cistanche (14)

Yog xav paub ntxiv:wallence.suen@wecistanche.com

Kev qaug zogyog ib qho mob uas nquag thiab tsis ua haujlwmuas tshwm sim hauv kwv yees li 80 feem pua ntawm cov neeg mob tau txais kev kho hluav taws xobthiab nyob rau hauv 24-30 feem puaCov neeg saib xyuas tsev neeg ntawm cov neeg mob qog noj ntshav (Swore Fletcher, Dodd, Schumacher, &Miaskowski, 2008). Txawm hais tias cov kws sau ntawv tau tshaj tawm txog qhov muaj ntau thiab tsis zoocuam tshuam ntawm cov tsos mob no rau ntau tshaj 30 xyoo, me ntsis paub txog cov txheej txheem uas underlieqaug zog.Thaum lub etiology ntawm qaug zog yog undoubtedly multifactorial, lub cev loj hlob ntawm pov thawjqhia tias txoj kev inflammatory yog ib qho tseem ceeb hauv kev txhim kho cov tsos mob no(Barsevick, Frost, Zwinderman, Hall, & Halyard, 2010; Jager, Sleijfer, & van der Rijt, 2008;Reyes-Gibby et al., 2008; Schubert, Hong, Natarajan, Mills, & Dimsdale, 2007).

Qhov tseeb,Ntau qhov kev tshawb fawb tau soj ntsuam rau kev koom tes ntawm cov ntshav cytokine qib thiab qaug zogtshwm sim los yog mob hnyav. Cov kev tshawb pom ntawm kev txheeb xyuas ntau (Schubert et al., 2007)qhia tias muaj kev sib raug zoo ntawm kev qaug zog thiab cov theem ntawm inflammatorycov cim. Txawm li cas los xij, ntawm 19 circulating inflammatory markers soj ntsuam, tsuas yog interleukin(IL)-6, IL1-receptor alpha (IL-1r ), thiab neopterin tseem ceeb nyob rau hauv qhov kev ntsuam xyuas zaum kawg.Cov kev tshawb pom tsis meej no tuaj yeem yog vim muaj cov teeb meem tshwm sim hauv kev ntsuas ntawmcirculating cytokines thiab rau circadian variability nyob rau hauv cytokine theem (Gilbertson-White,Aouizerat, & Miaskowski, 2011).

Ntxiv nrog rau cov kev tshawb fawb ntawm cov ntshav cytokines, ntau cov kev tshawb fawb tau sau cov koom haumntawm kev hloov pauv hauv cytokine noob thiab qaug zog (Aouizerat li al., 2009; Bower, Ganz,Irwin, Arevalo, & Cole, 2011; Collado-Hidalgo, Bower, Ganz, Irwin, & Cole, 2008; Hong thiabib., 1995; Miaskowski et al., 2010; Reinertsen et al., 2011). Hauv kev tshawb fawb ntawm 33 qaug zog thiab 14Cov neeg mob qog nqaij hlav cancer mis tsis nkees, Collado-Hidalgo li al. (2008) pom tias, thaumIL6yogtsis cuam tshuam nrog qaug zog,IL1Btau qhia ib lub koom haum. Hauv kev tshawb fawb los ntawm pebpab neeg tshawb fawb (Miaskowski li al., 2010), cov neeg mob oncology (n= 288) thiab cov neeg saib xyuas tsev neeg(n= 103) uas yog homozygotes rau cov allele hauvIL6rs4719714 qhia qib siab duathaum sawv ntxov thiab yav tsaus ntuj qaug zog thiab pw tsaug zog cuam tshuam.

Tsis tas li ntawd, nyob rau hauv no tib yampiv txwv, cov tib neeg uas yog homozygous rau ib qho allele hauv qog necrosis factor-alpha (TNFA)rs1800629 qhia txog qib siab dua thaum sawv ntxov nkees thiab pw tsaug zog(Aouizerat et al., 2009). Tib ib leeg nucleotide polymorphism (SNP) hauvTNFAyogcuam tshuam nrog cov tsos mob ntawm kev qaug zog thiab siab dua C-reactive protein ntau hauv cov neeg mobchronic fatigue syndrome (Jeanmonod, von Kanel, Maly, & Fischer, 2004). Hauv lwm txoj kev tshawb fawb,nyob rau hauv uas cov kws tshawb fawb piv fatigued (n= 11) thiab tsis nkees (n= 10) mob cancer missurvivors, nuclear factor kappa beta(NFKB)transcripts tau pom tias yuav nce ntawmfatigued survivors (Bower et al., 2011). Txawm li cas los xij, hauv txoj kev tshawb fawb loj ntawm cov neeg muaj mob qog noj ntshav mis,tsuas yog ib qho ntawm xya SNPs hauv tsib cytokine noob (piv txwv li, C-reactive protein[CRP]RS3091244)tau txuam nrog kev qaug zog (Reinertsen li al., 2011).

Ib qho ntawm cov kev txwv ntawm cov kev tshawb fawb tshawb fawb tau ua rau hnub no yog qhov kev hloov pauv hauv diurnalKev qaug zog hnyav thiab txuam nrog phenotypic thiab genotypic yam ntxwv tsis raug soj ntsuamhauv kev nthuav dav. Nyob rau hauv ib daim ntawv tsis ntev los no los ntawm peb pab neeg tshawb fawb siv kev loj hlob sib xyaw ua qauv(GMM) txhawm rau txheeb xyuas cov chav latent ntawm cov tib neeg uas muaj qhov sib txawv thaum sawv ntxov thiab yav tsaus ntujtrajectories ntawm cov neeg mob oncology thiab lawv tsev neeg cov neeg saib xyuas (Dhruva li al., 2013), pebpom phenotypic yam ntxwv uas txawv ntawm cov thaum sawv ntxov thiab yav tsaus ntuj qaug zogchav kawm. Piv txwv li, cov neeg koom hauv chav kawm High Morning Fatigue tau muaj feem ntau duahluas dua thiab muaj qhov ua haujlwm qis dua li cov neeg koom nrog hauv Low Morning Fatiguechav kawm. Piv txwv li, cov neeg koom hauv chav kawm High Evening Fatigue tau muaj feem ntau duahluas, poj niam, saib xyuas menyuam hauv tsev, thiab ib tsev neeg tu neeg dua li cov neeg koom hauvLow Evening Fatigue chav kawm. Tsis tas li ntawd, tsuas yog 10.3 feem pua ntawm cov qauv raug cais raws li nyob hauvob chav kawm thaum sawv ntxov thiab yav tsaus ntuj qis tshaj plaws thiab tsuas yog 41.3 feem pua ntawm cov qauv yogcais nyob rau hauv ob qho tib si siab tshaj plaws thaum sawv ntxov thiab yav tsaus ntuj chav kawm qaug zog. Raws li cov kev tshawb pom no,

peb tau hais tias kev qaug zog thaum sawv ntxov thiab yav tsaus ntuj tuaj yeem yog qhov txawv tab sis cov tsos mob ntsig txog.

Hauv daim ntawv no, peb txuas ntxiv cov kev tshawb pom no thiab ntsuas qhov sib txawv ntawm ntau tus pro-thiabanti-inflammatory cytokine noob ntawm cov neeg koom uas tau muab cais raws li muajqis thiab siab thaum sawv ntxov thiab yav tsaus ntuj qaug zog.

anti-fatigue function cistanche (12)

Yuav CISTANCHE rau kev kho CFS

Cov txheej txheem

Cov neeg koom nrog thiab Chaw

Cov ntsiab lus ntawm txoj kev tshawb no tau luam tawm lwm qhov (Aouizerat li al., 2009; Carney et al., 2011;Dhruva et al., 2012; Dunn et al., 2012; Miaskowski et al., 2010; Miaskowski et al., 2011). Hauvluv luv, cov neeg mob thiab lawv tsev neeg cov neeg zov me nyuam (FCs) raug xaiv los ntawm ob txoj kev kho hluav taws xobcov chaw haujlwm nyob hauv ib lub chaw kho mob kheesxaws thiab cov zej zog raws li oncologyqhov kev pab cuam thaum lub sij hawm ntawm cov neeg mob simulation mus ntsib.Cov neeg mob tau txais kev koom tes yog tias lawv loj dua lossis sib npaug li 18 xyoo; tau teem sijhawm kom tau txaisthawj los yog adjuvant radiation therapy rau ib qho ntawm plaub qhov kev kuaj mob qog noj ntshav (piv txwv li, lub mis, prostate,lub ntsws, los yog lub hlwb); tau nyeem, sau ntawv, thiab nkag siab lus Askiv; muab sau qhiakev tso cai; thiab muaj Karnofsky Performance Status (KPS) tau qhab nia siab dua lossis sib npaug li 60. Cov neeg mob tauTsis suav nrog yog tias lawv muaj kab mob metastatic, ntau tshaj ib qho kev kuaj mob qog noj ntshav, lossis kuaj pompw tsis tsaug zog. FCs tau tsim nyog los koom yog tias lawv siab dua lossis sib npaug rau 18 xyoo; muaj peev xwmnyeem, sau ntawv, thiab nkag siab lus Askiv; tau sau ntawv tso cai; tau KPS qhov qhab nia siab dua lossis sib npaug60; tau nyob nrog tus neeg mob, thiab tsis muaj kev kuaj mob pw tsaug zog.

Cov cuab yeej

Peb siv daim ntawv nug pej xeem kom tau txais cov ntaub ntawv hnub nyoog, poj niam txiv neej, kev txij nkawm,kev kawm, haiv neeg, kev ua haujlwm, thiab muaj ntau yam sib txawvtej yam kev mob. Peb kuj tau tshuaj xyuas cov ntaub ntawv kho mob rau cov kab mob thiab cov ntaub ntawv kho mob.Lee Fatigue Scale (LFS), uas peb tau siv hauv txoj kev tshawb no, muaj 13 yam khoomtsim los ntsuam xyuas lub cev qaug zog (KA Lee, Hicks, & Nino-Murcia, 1991). Tag nrho qaug zogqhab nia yog xam raws li qhov nruab nrab ntawm 13 yam khoom, nrog cov qhab nia siab dua qhia tias qaug zog ntau duahnyav. Cov neeg koom nrog raug nug kom ntsuas txhua yam khoom raws li lawv xav li cas "tam sim no" hauv30 feeb ntawm kev pw tsaug zog (kev qaug zog thaum sawv ntxov) thiab ua ntej yuav mus pw (kuj qaug zog). Lub LFStau zoo tsim validity thiab kev ntseeg tau. Hauv kev tshawb fawb tam sim no, Cronbach's alphas rauyav tsaus ntuj thiab sawv ntxov qaug zog ntawm kev tso npe yog {{0}}.96 thiab 0.95 rau cov neeg mob thiab 0.95 thiab 0.96rau FCs, feem.

Cov txheej txheem kawm

Txoj kev tshawb no tau pom zoo los ntawm Pawg Neeg Saib Xyuas Tib Neeg ntawm University ofCalifornia, San Francisco, thiab Institutional Review Board ntawm qhov chaw thib ob. Peb cawcov neeg mob koom nrog hauv txoj kev tshawb no kwv yees li 1 lub lis piam ua ntej pib tawgkev kho mob (piv txwv li, simulation mus ntsib thaum ntsuas kev kho hluav taws xob). Yog tiasFC tau tshwm sim, tus kws saib xyuas neeg mob tshawb fawb tau piav qhia txog txoj cai kawm rau tus neeg mob thiab FC,txiav txim kev tsim nyog, thiab tau txais kev tso cai sau ntawv. FCs uas tsis nyobtau hu xov tooj los txiav txim seb lawv puas txaus siab rau kev koom tes. Cov FCs no ua tiavcov txheej txheem rau npe kawm tom tsev. Cov neeg koom ua tiav LFS ntawm kev tso npe, 4 lub lis piamTom qab pib ntawm kev kho hluav taws xob, thaum ua tiav kev kho hluav taws xob, thiab ntawm 4, 8, 12,thiab 16 lub lis piam tom qab ua tiav kev kho hluav taws xob (piv txwv li, xya qhov kev ntsuam xyuas dhau 6hli).

Txoj kev tsom xam rau Phenotypic cov ntaub ntawv

Cov ntaub ntawv tau txheeb xyuas siv SPSS, version 19 (SPSS, 2010), thiab Mplus, version 6.11 (LKMuthen & Muthen, 1998-2010). Kev piav qhia txheeb cais thiab zaus faib tautsim los ntawm cov yam ntxwv ua piv txwv thiab cov qhab nia qaug zog. Kev ywj pheej qauv t-tests,Kev soj ntsuam ntawm qhov sib txawv (ANOVA), thiab Chi-square tsom xam tau ua tiav los ntsuas rauqhov sib txawv ntawm cov pej xeem thiab cov yam ntxwv kho mob ntawm cov chav kawm qaug zog.GMM nrog kev kwv yees qhov muaj peev xwm tshaj plaws tau siv los txheeb xyuas cov chav kawm latent (piv txwv li,pab pawg ntawm cov neeg koom nrog) nrog qhov sib txawv thaum sawv ntxov thiab yav tsaus ntuj qaug zog trajectories tshaj 6lub hlis ntawm kev kawm (BO Muthen & Kaplan, 2004). Vim tias 65 feem pua ntawm cov neeg koomHauv cov neeg mob-tus neeg saib xyuas dyads, cov qauv tau kwv yees nrog "dyad" raws li pawg sib txawv rauxyuas kom meej tias txhua qhov kev cia siab ntawm cov qhab nia thaum sawv ntxov thiab yav tsaus ntuj rau cov neeg mob thiabFCs hauv tib lub dyad tau tswj hwm rau hauv GMM tsom xam. Nws yuav tsum tau muab sau tseg tias tom qabnoj ib qho kev vam khom hauv dyads rau hauv tus account, tsis muaj qhov sib txawv tseem ceeb tau pomnruab nrab ntawm cov neeg mob thiab FCs nyob rau hauv parameter kwv yees rau ntau yam thaum sawv ntxov thiab yav tsaus ntuj

qaug zog GMM trajectories uas tau txheeb xyuas nyob rau hauv thawj zaug tsom xam.

Raws li tau tshaj tawm yav dhau los (Dhruva li al., 2013), peb chav kawm latent sib txawv tau txheeb xyuas rauthaum sawv ntxov thiab yav tsaus ntuj qaug zog. Rau cov neeg sib tw gene txheeb xyuas tau tshaj tawm hauv daim ntawv tam sim no,Cov chav kawm peb sawv ntxov qaug zog tau tawg ua ob pawg (piv txwv li, Tsawg heev [32.5 feem pua]piv rau qis thiab siab [67.5 feem pua]) raws li peb cov chav kawm qaug zog yav tsaus ntuj (piv txwv li, Tsawg [11.1 feem pua]piv rau Nruab Nrab thiab Siab [88.9 feem pua]). Qhov laj thawj rau qhov categorization no yog qhov tsawg heevtheem ntawm kev qaug zog thaum sawv ntxov thiab qis qis thaum yav tsaus ntuj qaug zog tuaj yeem xav tau nyob rau hauv dav davpej xeem. Txoj hauv kev zoo tshaj plaws-phenotype no yog ib lub tswv yim zoo los txheeb xyuas qhov muaj peev xwmCov noob caj noob ces cuam tshuam nrog cov tsos mob lossis kev kho mob (Li, Lewinger, Gauderman,Murcray, & Conti, 2011).

Kev kho tsis tau ua rau cov ntaub ntawv ploj lawm. Yog li ntawd, lub cohort rau txhua qhov kev ntsuam xyuas yognyob ntawm qhov loj tshaj plaws ntawm cov ntaub ntawv muaj nyob thoob plaws pawg. Ap-tus nqi ntawm <.05 yogsuav tias yog qhov tseem ceeb.

Methods of Analysis for Genomic Data

Gene xaiv -Pro-inflammatory cytokines txhawb kev mob o thiabsuav nrog interferon-gamma (IFN ), IB receptor 1 (IFN R1), IL-1R1, IL-2, IL-8, IL-17A,NFKB1, NFKB2, and TNF- . Anti-inflammatory cytokines inhibit qhov kev ua ntawm pro-inflammatory cytokines thiab suav nrog IL-1R2, IL-4, IL-10, thiab IL-13. Nco ntsoov, IFN 1, IB -1 , thiab IL-6 muaj cov yam ntxwv tiv thaiv kab mob (Seruga, Zhang, Bernstein, &Tannock, 2008).

Kev sau ntshav thiab genotyping -Genomic deoxyribonucleic acid (DNA) yogmuab rho tawm los ntawm archived buffy tsho loj siv PUREGene DNA Isolation System(Invitrogen, Carlsbad, CA). Ntawm 287 tus neeg koom nrog nrhiav, DNA tau zoo los ntawm 253cov neeg koom nrog (piv txwv li, 168 tus neeg mob thiab 85 FCs). Cov qauv raug genotyped siv GoldenGategenotyping platform (Illumina, San Diego, CA) thiab ua tiav siv GenomeStudio(Illumina, San Diego, CA).

Ib leeg nucleotide polymorphism (SNP) xaiv -Peb xaiv qhov sib xyaw ua ketagging SNPs thiab SNPs tawm tswv yim los ntawm cov ntaub ntawv rau kev tshuaj xyuas. Tagging SNPs tauyuav tsum muaj ntau (piv txwv li, txhais tau tias muaj qhov tsis tshua muaj allele zaus Ntau dua lossis sib npaug rau 0.05) hauv pej xeemdatabases. Txhawm rau kom ntseeg tau tias kev txheeb xyuas cov noob caj noob ces muaj zog, peb ua tau zootswj kev lim dej ntawm SNPs. SNPs nrog tus nqi hu <95 feem="" pua="" lossis="">p- tus nqi ntawm< .001="" were="">Raws li qhia nyob rau hauv ntxiv Table 1possible>, tag nrho ntawm 92 SNPs ntawm 15 tus neeg sib tw genes dhau tag nrho cov kev tswj xyuas zoothiab tau suav nrog hauv kev tshuaj ntsuam genetic Association (IFNG 1:5 SNPs;IFNGR1:1 SNP;IL1B:12 SNPs;IL1R1:5 SNPs;IL1R2:3 SNPs;IL2:5 SNPs;IL4:8 SNPs;IL6:9 SNPs;IL8:3 SNPs;TSI 10:8 SNPs;IB 13:4 SNPs;IB 17A:5 SNPs;NFKB1:11 SNPs;NFKB2: 4SNPs;TNFA:9 NPO). Muaj peev xwm ua haujlwm tau zoo ntawm SNPs cuam tshuam nrog tshwj xeebCov tsos mob tau kuaj xyuas siv PUPASuite 2.0 (Conde et al., 2006).

Statistical Analyses -Allele thiab genotype zaus tau txiav txim los ntawm cov noobsuav. Hardy-Weinberg equilibrium tau soj ntsuam los ntawm Chi-square lossis Fisher qhov tseebkuaj. Kev ntsuas ntawm kev sib txuas tsis sib xws (LD; piv txwv li, D' thiabr2) tau xam los ntawm covCov neeg koom nrog genotypes nrog Haploview

4.2. LD-based haplotype block txhais tau raws lintawm D' kev ntseeg siab lub sijhawm (Gabriel li al., 2002)

Haplotypes tau tsim los siv qhov program PHASE, version 2.1 (Stephens, Smith, &Donnelly, 2001). Tsuas yog cov haplotypes uas tau suav nrog qhov kev kwv yees kwv yees ntau dua lossis sib npaug rau .85hla tsib iterations tau khaws cia rau kev ntsuas qis qis. Haplotypes raug soj ntsuampiv txwv li tus qauv noj.

Cov cim qhia txog poj koob yawm txwv (AIMS) tau siv los txo qis kev ntxhov siab vimpejxeem stratification (Halder, Shriver, Thomas, Fernandez, & Frudakis, 2008; Hoggart etib., 2003; Tian, Gregersen, & Seldin, 2008). Homogeneity nyob rau hauv caj ces ntawm cov neeg koomtau txheeb xyuas los ntawm kev txheeb xyuas cov ntsiab lus tseem ceeb (Price et al., 2006) siv Helix Tree (GoldenHelix, Bozeman, MT). suav nrog hauv kev tshuaj ntsuam yog 106 AIMs. Thawj peb lub PC yogxaiv los kho qhov muaj peev xwm tsis meej pem vim cov pej xeem substructure (ie, haiv neeg /haiv neeg) los ntawm kev suav nrog peb covariates hauv txhua tus qauv regression.

Rau kev ntsuam xyuas kev koom tes, peb cov qauv caj ces raug soj ntsuam rau txhua SNP: additive, dominant,thiab recessive. Kev txhim kho tsis tseem ceeb (piv txwv li, delta <10 feem="" pua),="" cov="" qauv="" caj="" ces="" zoo="" tshaj="">haum cov ntaub ntawv, los ntawm maximizing qhov tseem ceeb ntawm covp-tus nqi, raug xaiv rau txhua SNP.Logistic regression tsom xam, uas tswj rau covariates tseem ceeb thiab rau haiv neeg/haiv neeg, tau siv los ntsuas kev sib koom ua ke ntawm genotype thiab qaug zog-pab pawgkev ua tswv cuab. Ib txoj hauv kev rov qab mus rau kauj ruam yog siv los tsim ib qho qauv parsimonious.

Tsuas yog rau tus kheej tshaj tawm haiv neeg / haiv neeg thiab AIMS, tsuas yog cov kwv yees nrog ap-tus nqi ntawm <.05tau khaws cia rau hauv tus qauv kawg. Genetic qauv haum thiab ob qho tib si unadjusted thiab covariate-khoQhov sib txawv ntawm qhov sib txawv tau kwv yees siv STATA version 9.Raws li tau ua tiav hauv peb cov kev tshawb fawb yav dhau los (Illi li al., 2012; McCann et al., 2012; C Miaskowski et al.al., 2012), raws li cov lus pom zoo hauv cov ntaub ntawv (Hattersley & McCarthy, 2005;Rothman, 1990), kev siv cov kev tswj xyuas zoo rau cov ntaub ntawv genomic, tsis muaj kev ywj pheejntawm SNPs / haplotypes hauv LD, thiab kev tshawb nrhiav qhov xwm txheej ntawm kev txheeb xyuas,

kev hloov kho tsis tau ua rau ntau qhov kev sim. Tsis tas li ntawd, tseem ceeb SNPs tau txheeb xyuas hauvcov kev ntsuam xyuas bivariate tau soj ntsuam ntxiv siv cov kev ntsuam xyuas regression uas tswj tausib txawv ntawm cov yam ntxwv phenotypic, muaj peev xwm confounding vim cov pejxeemstratification, thiab variation nyob rau hauv lwm yam SNPs / haplotypes nyob rau hauv tib lub noob. Tsuas yog covSNPs uas tseem ceeb tau suav nrog hauv qhov kev nthuav qhia zaum kawg ntawm cov txiaj ntsig.Yog li ntawd, cov koom haum ywj pheej tseem ceeb tshaj tawm tsis zoo li yuav yog vim tsuas yogcaij nyoog. Cov koom haum tsis tau hloov kho tau tshaj tawm rau txhua qhov SNPs dhau qhov kev tswj hwm zoo hauvNtxiv Table 1 kom tso cai rau kev sib piv tom ntej thiab kev tshuaj ntsuam meta.

Cov txiaj ntsig

Cov yam ntxwv koom nrog

Tag nrho cov qauv, uas yog 46.2 feem pua txiv neej thiab 53.8 feem pua poj niam, muaj 167 oncologycov neeg mob sab nraud thiab 85 FCs. Feem coob ntawm cov neeg tuaj koom tau kawm zoo thiab Caucasiannrog lub hnub nyoog nruab nrab ntawm 61.5 xyoo. Qhov qhab nia KPS yog 92 thiab cov neeg koom nrog nruab nrabntau tshaj plaub yam mob comorbid. Kwv yees li 49 feem pua ntawm cov neeg mob tau mob qog noj ntshav prostate,38 feem pua tau mob qog noj ntshav mis, 7 feem pua tau mob hlwb, thiab 6 feem pua tau mob qog noj ntshav. Peb nrhiav tsis tauQhov sib txawv tseem ceeb ntawm cov neeg mob 'thiab FCs' kev ntsuam xyuas ntawm kev qaug zog thaum sawv ntxov (2.3 ± 2.0piv rau 2.3 ± 1.9, ntsig txog) thiab yav tsaus ntuj qaug zog (4.2 ± 2.0 piv rau 4.5 ± 2.0, ntsig txog)ntawm kev tso npe kawm.

Phenotypic Qhov Sib Txawv Ntawm Cov Chav Kawm Thaum Sawv Ntxov

Piv rau cov nyob rau hauv chav kawm qis heev thaum sawv ntxov qaug zog (n= 82 [32.5 feem pua]), cov neeg koom hauvcov hoob Low and High classes (combinedn= 170 [67.5 feem pua]) tseem yau thiab muaj ib tugntau dua ntawm comorbidities thiab tus qhab nia KPS qis dua (Table 1). Hauv lubTsawg heev thaum sawv ntxov qaug zog chav kawm, peb pom tsis muaj qhov sib txawv ntawm cov neeg mob ({{0}}.7 ± 1.0) thiabFCs' ({{0}}}.9 ± 0.9) kev ntaus nqi ntawm kev qaug zog thaum sawv ntxov ntawm kev tso npe. Nyob rau hauv qhov qis thiab siab thaum sawv ntxovCov chav kawm qaug zog, peb pom tsis muaj qhov sib txawv ntawm cov neeg mob '(3.1 ± 1.8) thiab FCs' (3.0 ± 2.0)kev ntsuam xyuas ntawm kev qaug zog thaum sawv ntxov ntawm kev tso npe.

Cov neeg sib tw Gene tsom xam rau cov chav kawm thaum sawv ntxov Fatigue

Ntawm tsib SNPs uas txawv heev ntawm ob chav kawm qaug zog thaum sawv ntxov(Cov Lus Qhia Ntxiv 1), ob lub koom haum hauv ib lub noob tseem tseem ceeb hauv covmultivariate regression tsom xam (ie,TNFArs1800629, ua.TNFArs3093662). Rau ob qho tib si SNPs,tus qauv tseem ceeb haum cov ntaub ntawv zoo tshaj plaws (ob leegp = 0.006).

energy cistanche pillls (23)

Regression Analyzes of Candidate Genes for Morning Fatigue Classes

Yuav kom kwv yees zoo dua qhov loj (piv txwv li, qhov sib txawv piv txwv, LOSSIS) thiab qhov tseeb (95 feem puaKev ntseeg siab lub sijhawm, CI) ntawm genotype ntawm kev ua tswv cuab thaum sawv ntxov qaug zog, ntau yam sib txawvlogistic regression qauv tau haum los sib piv ob chav kawm. Ntxiv nrog rau genotype, lubCov yam ntxwv phenotypic uas tau suav nrog hauv cov qauv yog hnub nyoog, KPS qhab nia, thiab qhia tus kheejthiab genomic kwv yees ntawm haiv neeg / haiv neeg (Table 2).Nyob rau hauv lub regression tsom xam rauTNFArs1800629, ua heterozygous lossis homozygous rau lubTsis tshua muaj A allele (GG piv rau GA ntxiv rau AA) tau cuam tshuam nrog 52 feem pua ntawm qhov tsis sib xws ntawmteej tug mus rau pawg neeg qaug zog thaum sawv ntxov (Daim duab 1A). Nyob rau hauv lub regression tsom xam rauTNFArs309662, ua heterozygous lossis homozygous rau qhov tsis tshua muaj G allele (AA piv rau AGntxiv rau GG) tau txuam nrog 6.59-fold nce nyob rau hauv qhov sib txawv ntawm kev koom nrog ntau duapab pawg neeg qaug zog thaum sawv ntxov (Daim duab 1B).

Phenotypic Qhov Sib Txawv Ntawm Cov Chav Kawm Yav tsaus ntuj Fatigue

Piv nrog rau cov chav kawm qis thaum yav tsaus ntuj, cov neeg koom nrog hauv cov chav kawm nruab nrab thiab siabcov hluas heev, muaj qhov qhab nia KPS qis dua, thiab muaj feem ntau duamuaj menyuam nyob hauv tsev (Table 2). Hauv chav kawm Low night fatigue, peb pom tsis muajQhov sib txawv ntawm cov neeg mob '(1.2 ± 1.2) thiab FCs' (1.2 ± 0.8) kev ntsuas ntawm kev qaug zog yav tsaus ntuj ntawmkev tso npe kawm. Ib yam li ntawd, peb pom tsis muaj qhov sib txawv hauv nruab nrab thiab siab yav tsaus ntujCov chav kawm qaug zog ntawm cov neeg mob '(4.5 ± 1.8) thiab FCs' (4.8 ± 1.8) kev ntsuas ntawm kev qaug zog yav tsaus ntuj ntawmkev tso npe kawm.

Cov neeg sib tw Gene Analyzes rau yav tsaus ntuj Fatigue Classes

Ntawm yim SNPs uas txawv heev ntawm ob chav kawm qaug zog yav tsaus ntuj(Cov Lus Qhia Ntxiv 1), ib qho kev sib koom ua ke hauv ib qho ntawm ob lub noob tseem tseem ceeb hauv covmultivariate regression tsom xam (ie,IL 4r2243248 ,wb.TNFAr2229094). Rau ob qho tib si SNPs, atus qauv tseem ceeb haum cov ntaub ntawv zoo tshaj plaws.

Regression Analyzes ntawm Candidate Genes rau yav tsaus ntuj Fatigue Classes

Yuav kom kwv yees zoo dua qhov loj (ie, LOSSIS) thiab precision (95 feem pua CI) ntawm genotype ntawmyav tsaus ntuj qaug zog hauv chav kawm ua tswv cuab, ntau yam sib txawv logistic regression qauv tau haum raupiv ob chav kawm. Ntxiv nrog rau genotype, phenotypic yam ntxwv uas yogsuav nrog cov qauv yog hnub nyoog thiab qhia txog tus kheej thiab kev kwv yees genomic ntawm haiv neeg / haiv neeg(Table 3).Nyob rau hauv lub regression tsom xam rauIL 4rs2243248, ua heterozygous lossis homozygous rau qhov tsis tshua muajG allele (TT piv rau TG ntxiv rau GG) tau cuam tshuam nrog 70 feem pua txo qis hauv qhov sib txawv ntawm cov khoommus rau yav tsaus ntuj kev nkees nkees (Daim duab 2A). Nyob rau hauv lub regression tsom xam rauTNFArs2229094, ua heterozygous lossis homozygous rau qhov tsis tshua muaj C allele (TT piv rau TC ntxiv rau CC) yogcuam tshuam nrog 3.75-fold nce nyob rau hauv qhov sib txawv ntawm teej tug mus rau yav tsaus ntuj qaug zog duachav kawm (Daim duab 2B).

energy cistanche pillls (23)