食管癌易感性与白细胞介素-8基因多态性的关系

目的 探讨白细胞介素(IL)-8多态性与食管癌发生危险因素的关系.方法 采用以医院为基础的病例对照研究方法,以高分辨率熔解曲线(HRM)小片段扩增子法分析351例食管癌和384例非肿瘤对照IL-8基因多态性,计算各种基因型的食管癌发生风险及其95%可信区间.结果 IL-8-251(A/T)多态3种基因型TT、AT、AA在食管癌组和非肿瘤对照组的频率分别为39.9%(IT)、54.7%(AT)、5.4%(AA)和43.8%(TT)、45.3%(AT)、10.9%(AA),与携带IL-8-251TT基因型的个体比较,IL-8-251 AA等位基因型可以减少46%食管癌的发病风险.结论 IL-8-25l(A/T)基因多态性AA基因型可能是食管癌发生的保护性因素.

Abstract：

Objective To investigate the relationship between interleukin-8 (IL-8) polymorphism and the susceptibility to esophageal cancer in a Chinese Han population. Methods Genotypes were determined by the high resolution melting (HRM) method in 351 esophageal cancer cases and 384 controls without cancers. Results The IL-8 genotype frequency was 39. 9% ( TF), 54. 7% (AT), 5.4% (AA)in the esophageal cancer group, and 43.8% (TT), 45. 3% (AT), 10. 9% (AA) in the control group respectively. Logistic regression analyses revealed that the risk associated with IL-8 variant genotype was 0. 54 (95% CI =0. 30-0. 98) for IL-8 AA compared with its wild-type homozygote. Conclusion IL-8 AA polymorphism may serve as a protective biomarker of esophageal cancer susceptibility.     

白细胞介素16基因多态性与大肠癌发病风险的关系

目的：探讨中国山东籍汉族大肠癌（CRC）患者人群中,IL-16基因多态性与大肠癌发病风险的关系。 方法：在164例CRC患者和121名健康对照个体中,采用放大阻碍突变PCR（ARMS-PCR）方法对IL-16基因序列中的2个单核苷酸多态性（SNP）位点rs11556218和rs4778889进行基因分型,分析该2个位点的等位基因频率和基因型分布与CRC发病风险的关系。 结果：在CRC患者中,rs11556218的T/G等位基因频率和基因型分布与对照组的差异有统计学意义（P=0.021?725,P=0.001?033）;rs4778889的T/C等位基因频率及基因型分布与正常对照组的差异无统计学意义（P=0.057?946,P=0.064?229）。 结论：IL-16的rs11556218基因多态性与可能与CRC的易感性增加有关。     

Toll样受体7和9基因多态性与慢性丙型肝炎病毒感染的相关性

目的 分析慢性丙型肝炎病毒(HCV)感染与Toll样受体7(TLR7)和Toll样受体9(TLR9)单核苷酸多态性(SNP)的相关性.方法 选择2011年1月至2012年5月武汉大学人民医院150例慢性丙型肝炎(CHC)患者及同期体检的168名健康对照者.采用Sanger测序法检测TLR7IVS2-151(rs179009)基因型,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测TLR9T-1486C(rs187084)基因型.采用SPSS 15.0软件进行统计学分析,对基因型进行Hardy-Weinberg平衡吻合度检验.结果 TLR7 IVS2-151G频率在男性CHC患者中高于对照组男性(41.4％∶21.6％,x2=7.250,P=0.007,OR=0.389,95％ CI:0.194 ～0.781);TLR7 IVS2-151A的频率在女性CHC患者中显著高于对照组女性(76.9％∶63.1％,x2=7.202,P=0.007, OR=1.942,95％ CI:1.192 ～3.164).TLR9 T-1486C (rs187084)位点不同基因型和等位基因在CHC组和健康对照组间的分布频率差异均无统计学意义(P＞0.05).结论 TLR7 IVS2-151 (rs179009)位点与HCV感染存在相关性,其可能参与了CHC的发病.     

白细胞介素-22基因启动子区单倍体型与肺结核易感性的关联分析

目的 探讨白细胞介素-22(IL-22)基因启动子区单倍体型与肺结核易感性的关系.方法 收集2009年1月至2010年12月深圳市第三人民医院479例肺结核住院患者的资料,并以358名同期体检人员作为健康对照组.应用MassARRAY时间飞行质谱生物芯片技术检测各组的IL-22基因单核苷酸多态性(SNPs)(rs2227472、rs2227473、rs2227478、rs2227483、rs2227485、rs2227486、rs2227487和rs2227513)基因型,计算各SNPs位点及各单倍体型的等位基因频率及比值比(OR),分析IL-22基因单倍体型与肺结核易感性的关系.结果 SNPs位点rs2227472、rs2227473、rs2227478、rs2227483、rs2227485与结核易感性相关(OR值分别为0.796、0.653、0.769、0.762和0.816,x2值分别为4.594、6.921、5.256、5.089和3.827,P＜0.05或P＜0.01).IL-22基因单倍体型CTTAA(病例组频率0.004,健康对照组0.032)、TATGG(病例组频率0.522,对照组0.460)在两组人群中的频率差异有统计学意义(OR值分别为0.04和1.49,x2值分别为384.623和6.690,P＜0.01).结论 SNPs位点rs2227472、rs2227473、rs2227478、rs2227483和rs2227485与肺结核易感性相关.IL-22基因单倍体型CTTAA、TATGG与肺结核易感性相关,其中CTTAA为保护性单倍体型,TATGG为易感单倍体型.     

干扰素应答相关基因芯片在预测丙型肝炎抗病毒疗效中的应用研究

目的 探讨干扰素（IFN）应答相关基因在预测丙型肝炎抗病毒疗效中的作用.方法 采用功能分类基因芯片方法对IFN治疗前慢性丙型肝炎患者外周血单个核细胞（PBMC）IFN相关基因的表达进行检测,结合临床资料进行分析.采用SPSS 12.0软件进行统计学处理.结果 17例慢性丙型肝炎患者中,IFN治疗快速病毒学应答者（RVR）10例,非快速病毒学应答者（N-RVR）7例.与健康对照组比较,RVR患者PBMC中发现9个差异表达基因,其中1个为上调基因,8个为下调基因;N-RVR患者有18个差异表达基因,均为下调基因.RVR与N-RVR患者比较,发现5个差异表达基因,其中4个为上调基因,分别为PRKCZ、PRKRA、IRF5和TNFSF10（t=5.44、3.13、5.24和2.30,P=0.000、0.010、0.005和0.044）,1个下调基因为IFIT5（t=2.43,P=0.035）.17例患者中,12例为HCV1b型,5例为HCV2a型,HCV1b型与HCV2a型患者比较,发现2个下调基因,分别为IFI6和IFI44（t=2.42和2.45,P=0.038和0.033）.结论 IFN应答相关基因下调可能与慢性丙型肝炎患者对IFN治疗的应答有关.HCV1b型患者比HCV2a型患者更容易诱导IFN相关基因表达的下调,从而产生IFN抵抗.     

慢性丙型肝炎患者应用聚乙二醇干扰素α-2a和2b病毒学应答比较

目的 比较慢性丙型肝炎患者接受聚乙二醇干扰素α( Peg IFNα) -2a或Peg IFNα-2b联合利巴韦林治疗后的疗效差异.方法 对46例慢性丙型肝炎(CHC)患者进行回顾性分析,将患者分为2组,Peg IFNα-2a组24例,每周1次皮下注射Peg IFNα-2a 180μg,Peg IFNα-2b组22例,1...     

烫伤大鼠组织白细胞介素18和γ干扰素的表达

近年来研究表明 ,脓毒症的发病机制与多种炎性介质的过度产生有关 ,白细胞介素 (ＩＬ) 18作为一种新发现的致炎因子可能参与了严重创伤后的脓毒症过程。为此 ,我们采用大鼠烫伤模型 ,初步观察了烫伤后肠和肺组织中ＩＬ 18、γ 干扰素 (ＩＦＮ γ)ｍＲＮＡ表达的变化。一、材料和方法雄性Ｗｉｓｔａｒ大鼠 30只 ,随机分为正常对照组 (6只 ) ,烫伤组 (2 4只 )。烫伤组大鼠经 2 %戊巴比妥钠麻醉后 ,以2 0 %硫化钠脱毛 ,将动物背部浸入沸水中 12ｓ,致 30 %体表面积Ⅲ度烫伤。伤后 6ｈ腹腔注射林格液 40ｍｌ/ｋｇ抗休克。烫伤后观察时间为 :伤后 …     

白细胞介素-1O启动子区域627位基因多态性与乙型肝炎肝硬化的关系

目的研究IL-10启动子区627位点多态性与乙型肝炎肝硬化的关系。方法应用聚合酶链反应-限制性片段长度多态性（PCR—PFLP）等技术检测220例乙型肝炎肝硬化患者及200名健康对照者IL—10启动子627位等位基因及基因型频率的分布情况,分析其与肝硬化发病风险的相关性。结果IL—10启动子627位点AA和CA基因型及等位基因A在乙型肝炎肝硬化中的分布明显高于对照组（x^2=7．46、5．72和13．78,P值〈0．01或0．05）。结论IL-10启动子627位点基因多态性与乙型肝炎肝硬化相关。     

丙型肝炎病毒感染与IL28B多态性遗传关联研究进展

对HCV感染者的全基因组关联研究（genome—wide association studies,GWAS）发现,IL28B单核苷酸多态性（single nucleotide polymorphisms,SNPs）与急性HCV感染的病毒自发清除和抗病毒应答类型密切关联。IL28B多态性结合其他因素可预测HCV感染的转归。IL28B的编码产物干扰素（IFN）-λ3可通过类似于IFN-α的机制上调IFN刺激基因（IFN—stimulated genes,ISGs）的表达。本文综述了IL28B多态性与HCV各基因型之间的关联研究、临床应用及其机制。     

慢性丙型肝炎患者TLR3和TLR7mRNA表达及其与IL-27和病毒载量的关系

我国HCV感染率约为3．2％,高于世界平均水平。HCV感染者约70％将发展为慢性感染,其中部分慢性感染者可逐渐发展为肝硬化甚至肝细胞癌。Toll样受体（TLlt）是模式识别受体家族的重要一员,能够识别细菌、病毒、真菌、螺旋体、合成化合物及宿主的自身成分,参与激活白细胞、基质细胞以及活化B细胞、T细胞等过程,在先天性免疫和获得性免疫中发挥重要作用。     

Single nucleotide polymorphisms near IL28B gene and response to treatment of chronic hepatitis C in hemodialysis patients

Abstract

Background: It has been shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene were associated with sustained virological response following standard antivirological treatment of chronic hepatitis C. Objectives: The aim of the study was to evaluate the association between SNPs near the IL28B gene and response to the treatment of chronic hepatitis C in hemodialysis patients. Patients and methods: The study group included 24 hemodialysis patients with chronic hepatitis C routinely treated with pegylated interferon α-2?a. HCV genotype 1 was the cause of chronic hepatitis C in all study participants. Sustained virological response was determined by an assay with a sensitivity of 20?IU/mL, 6 months after completion of the antivirological treatment. The genotyping of the three most widely studied IL28B gene polymorphisms (rs12979860, rs8099917, and rs12980275) was performed in all study participants. Results: Sustained virological response was achieved in 50% of the treated patients. The treatment response was significantly associated with the CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 (p?=?0.003, p?=?0.009, and p?=?0.012, respectively). Conclusions: The three most widely studied SNPs near the IL28B gene were associated with sustained virological response following antivirological treatment of chronic hepatitis C in hemodialysis patients.     

Association of interleukin-18 promoter polymorphism and atherosclerotic diseases in Chinese patients with diabetic nephropathy

Aim: Interleukin‐18 (IL‐18) is a pro‐inflammatory cytokine and possibly plays an important role in the pathogenesis of cardiovascular disease. The relationship between two IL‐18 gene polymorphisms, namely C‐607A and G‐137C, and cardiovascular disease in patients with diabetic nephropathy was examined. Methods: Two hundred and twenty patients (91 male) with diabetic nephropathy were studied. The IL‐18 promoter genotypes were determined. All patients were then prospectively followed for the cardiovascular events. Cardiovascular mortality and all‐cause mortality were also compared. Results: Mean age was 64.3 ± 10.6 years; average follow up was 73.9 ± 33.6 months. The frequencies of CC, CA and AA genotypes of the C‐607A polymorphism were 25.5%, 48.2% and 26.8%, respectively; GG, GC and CC genotypes of the G‐137C polymorphism were 71.8%, 25.0% and 3.2%, respectively. Neither of the polymorphisms were associated with the development of primary cardiovascular end‐point. Cardiovascular survival was 84.8% and 70.6% at 60 months for GG and GC/CC genotypes of the G‐137C polymorphism, respectively (P = 0.027); the corresponding actuarial survival was 69.0% and 54.8%, respectively (P = 0.053). However, the G‐137C genotype was not an independent predictor of cardiovascular or actuarial survival after adjusting for confounders by multivariate analysis with the Cox model. The C‐607A polymorphism had no significant effect on cardiovascular or actuarial survival. Conclusion: The G‐137C polymorphism of the IL‐18 promoter is associated with the cardiovascular mortality, and a trend of association with all‐cause mortality, in patients with diabetic nephropathy. The association, however, becomes insignificant after adjusting for confounding factors. Further studies are needed to test other genetic determinants of the association between systemic inflammation and cardiovascular disease in renal failure patients.     

Seizures during the treatment with interferon for chronic C hepatitis

Interferon alpha (IFN-alpha) is a well-established first-line treatment for chronic viral hepatitis. Side effects of IFN-alpha therapy are common but generally mild and self-limited. Generalized seizures during IFN-alpha therapy are very uncommon and are present in clinical isolated cases and usually in association with high doses of IFN-alpha. In our case a female of 39 years old, seizures have occurred at low doses of IFN-alpha used as therapy for chronic C viral hepatitis. As it comes to our knowledge, till now, there were published only 4 cases of generalized seizures that occurred during treatment with IFN-alpha for chronic C viral hepatitis. The physiopathology of this complication is unknown. Generalized seizures can be reasonable due to IFN-alpha therapy, as long as the patient didn't have any seizure history, or other factors, which can develop seizures. Neurological examination, EEG and brain scan were normal. The recurrence of these seizures was absent stopping IFN-alpha therapy without any other seizure treatment.     

藏族人降钙素受体基因单核苷酸多态性和骨质疏松的关系

[目的]了解降钙素受体(Calcitonin receptor,CTR)基因单核苷酸多态性在藏族人中的分布规律及其与骨质疏松(Osteoporosis,OP)的相关性.[方法]利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法测定无亲缘关系的夏河县376名藏民的CTR基因型.并用UBIS 3000定量超声仪测定受试者超声振幅衰减(BUA)、超声声速(SOS)和刚度(STI)三项指标.[结果]受试者中TC型为25.8%、CC型为74.2%、未见TT型,男女间基因型差别无显著性意义(P＞0.1),TC基因型组的三项定量超声参数值高于CC基因型组,男性的BUA、SOS和STI均表现为极显著性差异(P＜0.001),女性的SOS和STI有显著性差异(P＜0.01),BUA有差异(P＜0.05).[结论]CTR的基因型具有种族差异性,藏族的CTR基因型分布频率不同于已见报道的其他种族,其CTR基因型与反映骨密度、骨强度和骨的结构特征的定量超声参数之间有一定关联,藏族的CTR基因型可能为影响骨质疏松发生的危险因素.     

Analysis of bronchoalveolar lavage fluid in patients with chronic hepatitis C before and after treatment with interferon alpha

BACKGROUND: Previous studies have shown that patients with idiopathic pulmonary fibrosis (IPF) were more likely to be seropositive for hepatitis C virus (HCV) than normal controls, and that patients with chronic hepatitis C treated with interferon alpha (IFN-alpha) sometimes developed pulmonary fibrosis. The possibility that HCV infection and/or treatment with IFN-alpha are involved in the pathogenesis of pulmonary fibrosis or alveolitis was investigated. METHODS: A prospective non- randomised study was performed in 13 healthy controls and in patients with chronic hepatitis C before (n = 13) and after (n = 10) treatment with IFN-alpha. Bronchoalveolar lavage (BAL) fluid cell counts, ratios and T cell subsets, and the concentrations of interleukin (IL)-1 beta, tumour necrosis factor(TNF)-alpha, and hepatocyte growth factor (HGF) were measured. RESULTS: Lymphocyte counts in the BAL fluid were significantly increased in both groups of patients (median (range) values: before treatment, 36.8 (1.5-226.0); after treatment, 16.2 (4.5- 97.6)) compared with the normal controls (3.3 (0.5-32.3)). In the pretreatment group the activated T cell (HLA-Dr positive) count was also increased (51 (40-74)) compared with that in the normal controls (27 (4-52)), but after treatment it was decreased (40 (0-76)) compared with the pretreatment count. Administration of IFN-alpha did not affect these parameters. IL-1 beta, TNF-alpha, and HGF were not detected. CONCLUSIONS: These findings suggest that HCV infection is associated with increased counts of lymphocytes and neutrophils in BAL fluid and that treatment with IFN-alpha appears to alter lymphocyte surface markers.


     

Sustained virological and histological response with pretransplant interferon therapy in renal transplant patients with chronic viral hepatitis C.

Patients who are anti-HCV positive before renal transplantation (Tx) have a significantly increased risk of posttransplant liver disease. We conducted a prospective, controlled study to evaluate the posttransplant outcome of renal graft candidates with HCV-associated chronic hepatitis (n = 30). Patients were randomly assigned to either of two groups. All patients on enrollment underwent liver biopsy, which showed mild-to-moderate hepatitis activity (mean 4.1, range 2-6). Half the patients received interferon-alpha (IFN-a) administered at a dosage of 3 million units three times weekly for 1 year. Liver biopsy was repeated for treated patients at the end of IFN-a treatment. Of these, 11 patients received renal transplant (group A). The other half did not receive IFN-a and to date 10 patients have been transplanted (group B). Renal transplant recipients were prospectively followed for a period of 12 months and a follow-up liver biopsy was also done at the end of this period (end of study). Biochemical and virological responses were evaluated and the histologic activity index (HAI) scoring according to Knodell was assessed. The mean pretreatment serum HCV RNA level was 1.14 +/- 0.84 and 1.0 +/- 0.89 mEq/ml for groups A and B, respectively (bDNA assay sensitivity threshold is <0.2 mEq/ml). HCV RNA became undetectable in 4 patients of group A. At the end of study period the mean quantitative HCV RNA titers were 1.43 +/- 4.07 and 15.18 +/- 11.08 mEq/ml in groups A and B, respectively (p < 0.0001). In group A, the mean HAI score decreased from 4.27 +/- 1.19 to 1.64 +/- 0.67 after IFN-a treatment (p < 0.0001). This score was maintained till the end of the study period with a mean of 1.82 +/- 0.6. Mean HAI score of group B on enrollment was 3.9 +/- 1.2 and at the end of study increased to 5.5 +/- 1.35 (p = 0.01). There was statistically significant difference (p value less than 0.0001) between the HAI scores at the end of the study period between the two groups. These results demonstrate that interferon therapy while on dialysis is associated with less viremia and decreased progression of chronic liver disease in renal transplant patients with hepatitis C.