精神分裂症IL-1βTNF-α基因多态性研究

【摘要】目的探讨白细胞介素-1β—511位点、＋3953位点和肿瘤坏死因子-α-308位点基因多态性与精神分裂症的关系及不同基因型对细胞因子分泌的影响。方法将161例精神分裂症患者设为精神分裂症组（患者组）,135名健康志愿者设为对照组。采用聚合酶链反应和限制性片段长度多态性技术检测白细胞介素1β在-511位点、＋3953位点及肿瘤坏死因子-α在-308位点的基因多态性;抽取患者组83例首发精神分裂症患者进行不同基因型细胞因子水平检测分析。结果在白细胞介素-1β-511位点,患者组基因GG型较对照组增高,但差异无显著性（P〉0．05）,等位基因G频率显著高于对照组（P〈0．05）;在白细胞介素-1β＋3953位点、肿瘤坏死因子-α-308位点,患者组基因型及等位基因频率与对照组比较差异均无显著性（P〉0．05）。在白细胞介素-1β-511位点和白细胞介素-1β＋3953位点,基因型G／A和AA的精神分裂症患者较GG型患者白细胞介素-1β水平明显增高（P〈0．05）;肿瘤坏死因子-α-308位点基因型G／A和AA的患者较GG型TNF-α水平明显增高（P〈0．05）。结论白细胞介素-1β-511位点、＋3953位点和肿瘤坏死因子-α-308位点基因多态性可能与精神分裂症无直接关联;白细胞介素-1β—511位点等位基因G可作为精神分裂症易感性的遗传标志之一;白细胞介素-1β—511位点和＋3953位点基因型G／A和AA为高分泌型,GG为低分泌型;肿瘤坏死因子-α-308位点基因型G／A和AA为高分泌型,GG为低分泌型。基因多态性影响细胞因子分泌。     

多次输血患者细胞因子基因多态性与发热性非溶血性输血反应的关联

细胞因子与包括发热性非溶血性输血反应(FNHTR)的炎症应答有关。而且,这些细胞细胞因子基因的多态性部分与不同水平基因表达有关。本研究目的在于调查多次输血患者FN-HTR发生与炎性细胞因子基因多态性的关联。作者研究了2组患者:一组在20次输入浓缩红细胞前发生FNHTR,而另外一组则即使经过20次输血后也从未发生FNHTR。通过对IL1B-511C/T、+3953C/T、IL1RN、(内含子2,可变数串联重复序列),IL6-174G/C、IL10-1082G/A和-819C/T、TNF-308G/A、LTA+253G/A基因片段以PCR及限制性酶切或测序的方法进行因子基因多态性研究。发…     

青岛地区哮喘患者IL-6基因启动子-634C/G位点多态性研究

目的:了解白细胞介素-6(interleukin-6,IL-6)基因启动子区域单核苷酸多态位点-634C/G与青岛地区汉族人群过敏性哮喘的相关性.方法:采用聚合酶链反应-限制性片段长度多态性分析方法对青岛地区479例健康个体和481例过敏性哮喘患者IL-6基因启动子-634C/G多态性进行观察.结果:过敏性哮喘组与健康对照组CC、CG和GG基因型以及C和G等位基因频率分布均无统计学差异,携带GG、CG、CC基因型个体哮喘患病风险依次递增.结论:IL-6基因启动子-634C/G位点多态性与青岛地区人群过敏性哮喘发生无相关性,但携带CC等位基因型的个体过敏性哮喘的发病风险可能增加.     

广西壮族人群TNF-α基因多态性及其表达与原发性肝细胞癌的相关性研究

目的探讨肿瘤坏死因子-α(TNF-α)-238/-308 2个位点的基因单核苷酸多态性(SNP)及血清TNF-α水平与广西壮族人群原发性肝细胞癌(HCC)的关系及其临床意义。方法将175名研究对象分为HCC组102例和正常对照组73名,采用双抗体夹心酶联免疫吸附试验(ELISA)和聚合酶链反应-限制性内切酶长度多态性(PCR-RFLP)技术检测血清TNF-α水平并对TNF-α-308/-238 2个位点基因多态性进行分型。结果 HCC组血清TNF-α水平显著高于正常对照组(P0.01),携带TNF-α-308 GA+AA基因型的个体血清TNF-α水平表达高于携带TNF-α-308 GG基因型个体(P0.01)。HCC组TNF-α-308位点的基因型和等位基因频率均高于正常对照组(P0.05),TNF-α-238位点的基因型和等位基因频率在HCC组和正常对照组中的分布差异均无统计学意义(P0.05)。携带TNF-α-308位点GA或AA基因型的个体与携带GG基因型的个体相比发生肝癌的风险更高[比值比OR=3.556,95%可信区间(CI)1.581~7.994],携带TNF-α-308 A等位基因的个体患HCC的风险是携带G等位基因个体的3.153倍(OR=3.153,95%CI 1.465~6.784)。结论 HCC患者的血清TNF-α水平高于正常对照组。TNF-α-308位点多态性与血清TNF-α水平有关。TNF-α-308位点多态性可能与广西地区壮族人群HCC的遗传易感性有关。     

miR-146a rs2910164 C>G基因多态性与先天性心脏病易感性的研究

目的研究中国汉族人群中miR-146a rs2910164 C>G基因多态性与先天性心脏病发生危险因素关系。方法采用以医院为基础的病例-对照研究,运用质谱SNP分型技术对120例法洛四联症(TOF)患儿,124例大动脉转位(TGA)患儿和136例对照人群进行了miR-146a rs2910164 C>G基因多态性分析,计算各种基因型的先心发生风险及其95%可信区间。结果 miR-146a rs2910164 C>G基因多态三种基因型CC,CG,GG在TOF组、TGA组以及对照组的频率分别为33.9%(CC),49.2%(CG),16.9%(GG);36.1%(CC),51.6%(CG),12.3%(GG)以及35.8%(CC),51.5%(CG),12.7%(GG);通过Logistic回归分析,发现携带miR-146a rs2910164 CG或GG等位基因型与TOF和TGA的发病风险无明显相关。结论 miR-146a rs2910164 C>G基因多态性可能不是先天性心脏病发生的危险因素,相关结果需要进一步研究证实。     

M型磷脂酶A_2受体和人类白细胞抗原基因单核苷酸多态性与维吾尔族特发性膜性肾病的相关性

目的探讨M型磷脂酶A_2受体(M-type phospholipase A_2receptor,PLA_2R)rs35771982和人类白细胞抗原(human leukocyte antigen DQα-chain 1,HLA-DQA1)rs2187668位点单核苷酸多态性与维吾尔族特发性膜性肾病(idiopathic membranous nephropathy,IMN)的相关性。方法 45例维吾尔族IMN患者为IMN组,45例同期维吾尔族体检健康者为对照组,采用直接测序法检测2组PLA_2R基因rs35771982、HLA-DQA1基因rs2187668位点单核苷酸多态性(single nucleotide polymorphism,SNP),比较2组基因型和等位基因频率;采用单因素logistic回归分析风险基因型。结果 IMN组PLA_2R基因rs35771982位点C等位基因频率(78.90%)明显高于对照组(40.00%)(P0.01);在显性模型下PLA_2R基因rs35771982位点携带CC基因型的患病风险为携带CG+GG基因型的7倍(OR=7.00,95%CI:2.74~17.87,P=0.000),隐性模型下携带GG基因型的患病风险为携带CC+CG基因型的0.13倍(OR=0.13,95%CI:0.04~0.44,P=0.000);IMN组PLA_2R基因rs35771982位点CC基因型血清肌酐[103.15(74.28,175.67)μmol/L]和24h尿蛋白[2.77(2.00,3.95)g]明显高于CG+GG基因型[73.70(58.87,106.65)μmol/L、1.90(1.39,2.75)g](P0.05),收缩压[(138.03±23.11)mmHg]高于CG+GG基因型[(123.13±15.05)mmHg],血清白蛋白[26.80(17.84,28.86)g/L]明显低于CG+GG基因型[29.96(25.67,36.64)g/L](P0.05);2组HLA-DQA1SNP rs2187668位点仅检测到GG基因型,未检测到GA、AA基因型。结论 PLA_2R基因rs35771982位点CC基因型和C等位基因是新疆维吾尔族IMN的易感基因,也是功能基因,其中CC基因型与尿蛋白定量呈正相关,与血清白蛋白水平呈负相关。     

转化生长因子-β1基因多态性与乙型肝炎病毒慢性感染发展至肝细胞癌风险的相关研究

目的：探讨转化生长因子-β1基因多态性与乙型肝炎病毒（HBV）慢性感染发展至肝细胞癌风险的关系。方法随机纳入120例 HBV 慢性感染患者（病例组）和100例与病例组性别、年龄相匹配的健康者（对照组）,并将病例组分为非肝癌组和肝癌组。采用聚合酶链反应-限制性片段长度多态性分析法检测各组 TGF-β1基因多态性（T29C）并结合 TGF-β1 mRNA 水平进行比较分析。结果携带基因型 CC 发生肝癌的风险较携带基因型 TT 显著降低（OR ＝0．317,95％CI ＝0．110～0．913,P ＝0．033;OR＝284,95％CI ＝0．093～0．866,P ＝0．027）。携带等位基因 C 较等位基因 T 发生肝癌的风险显著降低（OR ＝0．570,95％CI ＝0．341～0．953,P ＝0．032;OR＝0．548,95％CI ＝0．320～0．936,P ＝0．028）。肝癌组中携带基因型 CC 的患者 TGF-β1 mRNA 水平较低。结论TGF-β1基因 T29C 多态性可能与 HBV 慢性感染进展至肝细胞癌风险有关。     

脂联素基因-11377C/G多态性与缺血性脑卒中的相关性

[目的]探讨脂联素基因(ADIPOQ)-11377C/G多态性与缺血性脑卒中的相关性.[方法] 用聚合酶链式反应-限制性片段长度多态性方法检测302例缺血性脑卒中患者和338例健康对照者的ADIPOQ基因-11377C/G位点的基因型.[结果]①病例组的GG基因型和G等位基因频率明显高于对照组(P=0.034和P=0.010).②GG基因型携带者发生缺血性脑卒中的危险是CC基因型携带者的2.062倍(95%CI:1.145~3.715;P=0.016),校正各种混杂因素后发病危险度为2.165倍(95%CI:1.116~4.197;P=0.022).③-11377C/G位点与动脉粥样硬化性脑梗死的发病有关,与腔隙性脑梗死的发病无关.[结论] ADIPOQ基因的-11377C/G位点的GG基因型和G等位基因可能增加缺血性脑卒中的发病风险,特别是动脉粥样硬化性脑梗死的发病风险,其可能是缺血性脑卒中的危险因素.     

冠心病患者血管内皮生长因子+450C/G基因多态性研究

目的探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)基因多态性与冠心病的关系。方法应用PCR-限制性片段长度多态性方法检测249例冠心病患者(冠心病组)和99例体检健康者(对照组)VEGF基因+450C/G基因位点及基因分型,比较冠心病不同基因型患者血清VEGF水平。结果 VEGF基因+450C/G有3个基因型(CC、CG、GG型),冠心病组CC基因型频率(25.3%)和C等位基因频率(50.8%)明显高于对照组(11.1%、35.9%)(P0.05),GG基因型频率(23.7%)和G等位基因频率(49.2%)低于对照组(39.4%、64.7%)(P0.05),CG基因型频率(51.0%)与对照组(49.5%)比较差异无统计学意义(P0.05);冠心病组CC基因型患者血清VEGF水平[(702.78±122.46)ng/L]明显高于CG基因型[(601.36±131.32)ng/L)]和GG基因型[(487.25±147.29)ng/L],CG基因型高于GG基因型(P0.05)。结论 VEGF+450C/G基因多态性可能与冠心病的发生、发展有关,C等位基因可能是冠心病血管病变的易感基因。     

内皮一氧化氮合酶基因多态性与先天性心脏病易感性的研究

目的:研究中国汉族人群中内皮一氧化氮合酶(endothelial nitric oxide synthase,eNOS)rs1799983G>T基因多态性与先天性心脏病易感性的关系。方法:采用以医院为基础的病例-对照研究,采用基质辅助激光解吸电离飞行时间质谱(matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,MALDI-TOFMS)技术分析120例法洛四联症(tetralogy of fallot,TOF)患者(TOF组)、124例大动脉转位(transposition of the great arteries,TGA)患者(TGA组)和136例非先天性疾病患者(对照组)eNOSrs1799983G>T基因多态性,计算各种基因型的先天性心脏病发生风险及其95%可信区间。结果:eNOSrs1799983G>T基因多态三种基因型GG、GT、TT在TOF组、TGA组和对照组的频率分别为77.1%(GG)、21.2%(GT)、1.7%(TT),80.5%(GG)、19.5%(GT)、0%(TT)和82.2%(GG)、17.8%(GT)、0%(TT),Logistic回归分析发现与携带eNOSrs1799983GG基因型的个体相比较,携带eNOSrs1799983GT等位基因型与TOF和TGA的发病风险无明显相关[(OR=1.27,95%CI=0.68～2.37)和(OR=1.12,95%CI=0.60～2.10)]。结论:eNOSrs1799983G>T基因多态性可能不是先天性心脏病发生的危险因素,需要进一步研究证实。     

The association of cytokine gene polymorphisms with febrile non-hemolytic transfusion reaction in multitransfused patients

Cytokines are associated with inflammatory responses including febrile non-hemolytic transfusion reactions (FNHTR). Moreover, there are some polymorphisms of these cytokine genes associated with different levels of gene expression. The aim of the present study was to investigate the association of inflammatory cytokine gene polymorphisms with the occurrence of FNHTR in multitransfused patients. We studied two groups of transfused patients: one presenting FNHTR before 20 transfusions of red blood cells concentrates and the other which never presented FNHTR even after 20 transfusions. The gene polymorphisms studied were IL1B-511C/T and +3953C/T, IL1RN (intron 2, variable number tandem repeat), IL6-174G/C, IL10-1082G/A and -819C/T, TNF-308G/A and LTA+253G/A using polymerase chain reaction and restriction digestion or sequencing methods. An association of IL1RN*2.2 genotype with the occurrence of precocious FNHTR (P < 0.025) was detected. This allele and this genotype have been related with higher serum levels of interleukin (IL)-1beta in vivo and higher promoter activity. No other association was demonstrated. The association of gene polymorphisms related with the increase of inflammatory cytokine gene expression may be a relevant factor in FNHTR and requires confirmation.     

Proinflammatory cytokine gene polymorphisms among Hashimoto's thyroiditis patients

Proinflammatory cytokines are involved in the pathogenesis of Hashimoto's thyroiditis (HT). To test whether certain specific proinflammatory cytokine gene polymorphisms could be genetic markers for an individual's susceptibility to HT, we investigated single-site polymorphisms of certain proinflammatory cytokine genes of interest for 107 HT sufferers and 163 controls, subsequent to preparing the necessary experimental genomic DNA from peripheral blood, using a polymerase chain reaction (PCR)-based restriction analysis. The polymorphisms we detected were as follows: 1) C/T and E1/E2 polymorphisms for the interleukin (IL)-1beta gene at promoter (-511) and exon 5, respectively; 2) a variable number of tandem repeats (VNTRs) for the IL-1 receptor antagonist (IL-1Ra) gene at intron 2; 3) a C/G polymorphism for the IL-6 gene at promoter (-572); and 4) an A/G polymorphism for the tumor necrosis factor (TNF)-alpha gene at promoter (-308). The data demonstrated an increased ratio of CG genotype and decreased ratios of CC and GG genotypes (chi-squared test; P = 0.025) for the IL-6 gene promoter for HT patients when compared with normal controls. The odds ratio (OR) for the CG genotype, as compared to the GG genotype, for HT patients was shown to be 4.065 (95% confidence interval (CI): 1.268-13.032). Comparison of the genotype analysis for the remaining gene polymorphisms and the allelic analysis for all of the screened gene polymorphisms, however, all revealed no statistically significant difference between the two study groups as regards frequency of genotype. In conclusion, we suggest that an IL-6 gene promoter (-572) C/G polymorphism could represent a potential "candidate" genetic marker to predict an individual's susceptibility to HT.     

Influences of proinflammatory and anti-inflammatory cytokine polymorphisms on eradication rates of clarithromycin-sensitive strains of Helicobacter pylori by triple therapy

BACKGROUNDS AND AIMS: Polymorphisms of proinflammatory cytokines, such as interleukin (IL) 1beta and tumor necrosis factor (TNF) alpha, are associated with individual differences in gastric mucosal inflammation and acid inhibition in response to Helicobacter pylori infection. We investigated whether inflammation-related cytokine polymorphisms would influence the eradication rates of H pylori by a triple-therapy regimen. METHODS: Three hundred sixty patients infected with clarithromycin-sensitive strains of H pylori were genotyped for IL1B -511, IL1RN, TNFA -857/-863/-1,031, IL10 -1,082/-819/-592, and CYP2C19 and underwent triple therapy for 1 week with a proton pump inhibitor (20 mg omeprazole, 30 mg lansoprazole, or 10 mg rabeprazole) twice daily, 400 mg clarithromycin twice daily, and 750 mg amoxicillin (INN, amoxicilline) twice daily. The influences of the previously mentioned polymorphisms on the eradication rates were analyzed. RESULTS: The intention-to-treat-based total eradication rate was 83.6% (301/360). The logistic regression analysis revealed that polymorphisms of CYP2C19 and IL1B -511 were independently associated with the eradication rates, but other cytokine polymorphisms were not associated with these rates. The eradication rates in patients with IL1B -511 C/C, C/T, and T/T genotypes were 72.2% (70/97), 87.7% (164/187), and 88.2% (67/76), respectively (P = .0017). When patients were stratified by CYP2C19 genotype status, IL1B -511 genotype-dependent differences in eradication rates were observed in homozygous extensive metabolizers (EMs) but not in heterozygous EMs and poor metabolizers of CYP2C19. The eradication rate in homozygous EM patients with the IL1B -511 C/C genotype was quite low (51.1% [22/43]). CONCLUSIONS: IL1B -511 polymorphism, but not IL1RN, TNFA, or IL10 polymorphism, is one of the determinants of triple therapy for clarithromycin-sensitive strains of H pylori in CYP2C19 homozygous EMs.     

Relationships of interleukin-17 polymorphisms with recurrent aphthous ulcer risk in a Han Chinese population

ObjectiveInterleukin (IL)-17 is a multifunctional cytokine with important roles in inflammatory and autoimmune diseases. This case–control study explored the relationships of IL-17A rs2275913 and IL-17F rs763780 single-nucleotide polymorphisms (SNPs) with recurrent aphthous ulcer (RAU) morbidity and severity.MethodsIL-17A rs2275913 and IL-17F rs763780 SNPs were measured in 125 patients with RAU and 116 healthy control participants. The genotype distributions, disease risks, and relationships with RAU severity were analyzed.ResultsRAU risk was associated with rs2275913 after adjustment for age, body mass index, sex, smoking status, and drinking status (AA vs. GG: odds ratio [OR], 2.759; 95% confidence interval [CI], 1.381–5.512; A allele vs. G allele: OR, 1.783; 95% CI, 1.242–2.560). TC and CC genotypes in rs763780, and the corresponding C allele, demonstrated greater prevalence among patients with RAU, compared with the TT genotype (TC vs. TT, OR: 1.895; 95% CI: 1.088–3.301; CC vs. TT, OR: 4.080, 95% CI: 1.079–15.425; C allele vs. T allele, OR: 1.969, 95% CI: 1.257–3.083). Serum IL-17 concentrations were also higher in patients with RAU than in control participants. These concentrations were associated with IL-17 polymorphisms.ConclusionsIL-17 polymorphisms might be associated with greater risk of RAU pathogenesis.     

Genetic factors that influence short-term neurodevelopmental outcome in term hypoxic-ischaemic encephalopathic neonates

It is difficult to predict outcome in neonates that experience perinatal hypoxic ischaemia. Morbidity and mortality may be affected by genetic factors that augment inflammatory and coagulative responses. This prospective study analysed the effects of proinflammatory cytokine gene polymorphisms (tumour necrosis factor-α [TNFA] 308G>A and interleukin-6 [IL6] 174G>C) and prothrombotic factor gene mutations (prothrombin G20210A, factor V Leiden G1691A and methylenetetra hydrofolate reductase [MTHFR] C677T) on the early neurological prognosis in 40 term hypoxic ischaemic encephalopathic neonates. There were significant relationships for Sarnat and Sarnat staging with electroencephalographic findings, transfontanelle ultrasound (US) results, early neonatal outcome and neurological morbidity. Genetic mutations in the prothrombotic proteins, the TNFA 308G>A polymorphism and the cerebrospinal fluid levels of TNF-α protein were not related to clinical stage, electroencephalography, transfontanelle US or neurological status at discharge or at postnatal months 6 and 12. The IL6 174GC genotype demonstrated a protective role, being significantly correlated with normal electroencephalography, transfontanelle US and normal neurological findings at discharge. In conclusion, the IL6 174GC gene polymorphism seems to play a role in determining the risk and/or severity of perinatal cerebral injury.     

Interleukin-6 gene promoter -174G/C polymorphism and insulin resistance: a pilot study.

BACKGROUND: The aim of this pilot study was to evaluate the relationship between interleukin-6 promoter -174G/C (IL-6 -174G/C) polymorphism and insulin resistance (IR) in obese patients with coronary heart disease (CHD). METHODS: Twenty obese male patients with CHD were selected from a larger database of patients (n=606). IL-6 -174G/C genotype was previously analysed and only homozygotes with the CC genotype (n=10) or GG genotype (n=10) were selected. IR was measured using the homeostasis model assessment for IR (HOMA-IR) method. RESULTS: Differences in age, body mass index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), hypertension, IL-6, C-reactive protein and HOMA-IR were not significant between the genotypes (p>0.05), but analysis of a homogeneity-of-slopes model showed that genotype had a significant influence on HOMA-IR (p=0.037), and the interaction between genotype and HDL-C had a pronounced tendency to affect HOMA-IR (p=0.058). Using multiple regression analysis, we found that HDL-C had a significant effect on HOMA-IR (p=0.023), and TG had a tendency to affect HOMA-IR (p=0.066) only in the CC genotype. CONCLUSIONS: Our data show that IL-6 -174G/C polymorphism may have a significant effect on IR. A comparison between the effects of various cardiovascular risk factors showed that HDL-C may have a significant effect on HOMA-IR in the CC genotype but not in the GG genotype. Further research is needed to test the preliminary results.     

Tumor necrosis factor-alpha -308 gene polymorphism is associated with synthetic hemodialysis graft failure.

BACKGROUND: Progressive venous stenosis mediated, in part, by inflammatory cytokines is a major cause of synthetic hemodialysis graft failure. A tumor necrosis factor-alpha (TNF-alpha) gene polymorphism (G to A, position -308) has been shown to increase plasma cytokine levels and severity of diseases with an underlying inflammatory component. METHODS: We genotyped 67 patients with synthetic polytetrafluoroethylene (PTFE) grafts and examined the association of the high-(AA or GA) and low- (GG) production TNF-alpha-08 genotypes with the rate of graft failures/thrombosis and graft survival. RESULTS: Hemodialysis patients with the high-production TNF-alpha genotypes had a significantly increased rate of PTFE graft failure at 90 days (37.2% versus 14%) and 1 year (62.8% versus 34.4%) after graft placement compared with patients with the low-production genotype (respectively). Hemodialysis patients with the high-production TNF-alpha genotypes had significantly lower cumulative PTFE graft survival at 1 year (29.4% +/- 11.1% versus 71.2 +/- 6.8%) and 2 years (22.1% +/- 10.5% versus 48.2 +/- 8.1%) compared with patients with the low-production genotype (respectively). Patients with the A allele had approximately twice the mean thrombosis rate compared with those who had the low-production TNF-alpha genotype (3.3 +/- 0.8 versus 1.7 +/- 0.4 thromboses/patient/year, respectively; mean +/- SEM, p < .05). CONCLUSIONS: These data suggest that the TNF-alpha -308 A allele is associated with increased PTFE graft thrombosis and failure in hemodialysis patients.     

Extremely high interleukin-6 blood levels and outcome in the critically ill are associated with tumor necrosis factor- and interleukin-1-related gene polymorphisms

OBJECTIVE: To determine the allelic frequencies of interleukin (IL)-6-, IL-1-, and tumor necrosis factor-alpha (TNF)-related gene polymorphisms in critically ill patients with extremely high IL-6 blood level and to examine the genetic effects on their clinical courses. DESIGN: Population-based association study. SETTING: A general intensive care unit in a university teaching hospital. PATIENTS: A total of 150 consecutive critically ill patients recruited at admission to the intensive care unit, regardless of diagnosis, and 150 healthy volunteers. MEASUREMENTS AND MAIN RESULTS: IL-6 blood levels were measured daily with chemiluminescence immunoassay. The IL-6 peak levels were significantly correlated with simultaneously measured TNF (r = .659, p < .0001) and IL-1beta levels (r = .518, p < .0001), respectively. Single nucleotide polymorphism at position -174 and -596 sites of the IL-6 (IL6-174*G/C and IL6-596*G/A), -308 site of the TNF (TNF-308*G/A), and -511 site of the IL-1beta (IL1B-511*C/T) were identified with real-time polymerase chain reaction assay using specific fluorescence-labeled probe. Within the IL-1 receptor antagonist intron 2, a various number of tandem repeat polymorphisms (IL1RN*1-5) were identified after polymerase chain reaction with gel electrophoresis. Allelic frequencies of patients with IL-6 peak levels of > or =10,000 pg/mL (group A) were compared with those of patients with IL-6 peak levels of <10,000 pg/mL (group B). Neither IL6-174*C nor IL6-596*A were recognized in all the subjects; however, group A showed a higher frequency of TNF-308*A (p = .054), IL1B-511*T (p = .013), and non-IL1RN*1 (p = .008) allele compared with group B. TNF-308*A, IL1RN*2 or IL1RN*3 allele carriers of group A showed sustained high IL-6 levels, despite countermeasures against hypercytokinemia, and their survival rate was lower than that of the noncarriers of those high-risk alleles (p = .025). CONCLUSIONS: TNF-308*A, IL1RN*2, and IL1RN*3 alleles were associated with the prevalence of the extremely high IL-6 blood level in the critically ill, their uncontrollable blood IL-6 kinetics, and outcome.     

炎症因子与乳腺癌患者辅助放射治疗期间癌性疲劳的相关性

目的探讨炎症因子与乳腺癌患者辅助放射治疗期间癌性疲劳的相关性。方法选取术后辅助放射治疗的乳腺癌患者,按埃德蒙顿症状评估系统的疲劳评分将其分为疲劳组及观察组,比较2组血清炎症因子CRP、IL-6及可溶性肿瘤坏死因子受体2(sTNFR2)的差异;检测每位患者的疲劳相关炎症因子编码基因启动子的单核苷酸多态性,分析炎症因子相关基因分型与放射治疗结束时疲劳评分的相关性。结果共61例患者入组,其中疲劳组37例。观察组24例,癌性疲劳的发生率为60.6%。疲劳组伴有恶心、焦虑及厌食者较观察组多(P均<0.05)。疲劳组放射治疗后血清IL-6水平较治疗前高(P <0.001),观察组放射治疗前、后IL-6水平比较差异无统计学意义(P> 0.05)。IL-6水平与疲劳的发生呈正相关(r_s=0.51,P <0.001)。2组治疗前后CRP及sTNFR2水平比较差异均无统计学意义(P均> 0.05)。IL-6启动子编码基因IL6-174 GG基因分型的乳腺癌患者放射治疗结束时的疲劳评分高于CC基因分型患者(P=0.001)。结论血清IL-6水平及IL6-1...