凋亡信号通路基因多态性与煤工尘肺易感性

目的 探讨凋亡信号通路基因细胞凋亡基因(FAS)、FAS配体基因(FASL)、半胱氨酸-天冬氨酸蛋白质酶(CASP8)及CASP3单核苷酸多态性(SNP)与煤工尘肺易感性的关系.方法 采用病例-对照的研究方法,选择511例煤工尘肺患者为病例组,530例同单位、同工种、且工龄相近、未患尘肺的煤尘接触者为对照组;聚合酶链反应-限制性片段长度多态性( PCR-RFLP)法检测5个SNP位点的基因型;CASP3 rs 6948位点用荧光定量PCR法进行基因分型.结果 煤工尘肺组和对照组6个多态性位点的各基因型的分布频率比较,差异无统计学意义(P＞0.05).CASP8-652位点的6个碱基缺失(DD型)可明显增加煤工尘肺患病的危险性(调整后OR=1.96,95％ CI=1.15～3.33,P=0.013),其他各基因型对煤工尘肺患病危险性没有明显的影响;对CASP8-652 I＞D基因多态性进行分层分析发现,工龄≥28年组、吸烟组及1期煤工尘肺携带CASP8-652 DD基因型者煤工尘肺的患病危险性明显增高,差异有统计学意义(P＜0.05).6个多态性位点不同基因型之间的相互作用与煤工尘肺患病的关联性分析发现,携带FAS-1377GG/CASP8-652DD型者、携带FAS-670AG/CASP8-652DD型者和携带FASL-844CT/CASP8-652DD型者煤工尘肺患病危险性明显增加;携带FAS- 1377GA/CASP8-652ID型者煤工尘肺患病危险性明显降低.对Ⅰ期煤工尘肺患者中CASP8-652位点II、ID、DD 3种基因型携带者发病前的粉尘暴露时间进行回归分析,差异无统计学意义(P＞0.05).Ⅰ期煤工尘肺患者中不同基因型携带者发病前的粉尘暴露时间比较,差异无统计学意义(P＞0.05).结论 CASP8-652缺失基因型在煤工尘肺病变的发展过程中可能起一定的作用,并且与FAS- 1377、FAS-670及FAL-844存在基因相互作用.     

凋亡相关基因FAS-1377和FAS-670及其配体FASL-844位点基因多态性与中国汉族煤工尘肺的关系

目的探讨FAS／FASL基因多态性在煤工尘肺患者发病遗传易感性中的作用及其与煤工尘肺纤维化程度的联系。方法选择340例汉族煤工尘肺为观察对象，312例汉族煤尘接触者为对照组，应用多聚酶链反应-限制片段多态性（PCR—RFLP）技术检测FAS-1377G〉A、FAS-670A〉G位点及FASL-844T〉C位点的基因多态性。结果煤工尘肺组FAS．1377、FAS-670及FASL-844各基因及等位基因分布频率与对照组比较，差异无统计学意义（乃0．05）。以接尘工龄／〉25年为对照，工龄〈25年的煤工尘肺患者FAS-1377GA／AA型者发生尘肺的危险性是GG型的1．463倍（P=0．098，95％CI：0．932～2．298）；FAS-670AG型发生尘肺的危险性是GG型者的1．494倍（P=0．098，95％C／：0．928～2．404）：FASL-844TT型和TC型发生尘肺的危险性分别是CC型的5,455倍（P=0．039，95％CI：1,088-27．358）及1,338倍（P=0．098，95％CI：0．852-2．101）。接尘工龄〈25年FASL-844基因分布频率和工龄≥25年比较，差异有统计学意义（P〈0．05），FASL-844Tr型发生煤工尘肺的危险性是CC／TC型的4．810倍（P=O．054，95％CI：0．971-23．833）；接尘工龄≥25年为对照，工龄〈25年组FASL-844TT／CT＋FAS-1377GA型发生煤工尘肺的危险性是FASL-844CC＋FAS-1377GG型的1．810倍；FASL-844TT／CT＋FAS．670AG型是FASL-844CC＋FAS-670AA型的2．117倍；FASL-8TT／CT＋FAS-1377GA／AA＋FAS-670AG／GG型发生煤工尘肺的危险性是FASL-844CC＋FAS-1377GG＋FAS-670AA型的2．043倍。结论FAS．1377G〉A、FAS-670A〉G及FASL-844T〉C3个位点的基因多态性在中国汉族煤工尘肺发病的遗传易感性中不起主要作用，但这3个多态性位点及位点的联合作用对病变的发展有影响。     

Polymorphisms in the promoter of the tumor necrosis factor-α gene in coal miners

Tumor necrosis factor-α (TNF) is recognized as a central mediator of mineral dust-induced lung fibrosis, and genetic polymorphisms of the TNF promoter have been reported to influence levels of TNF production. To assess whether polymorphisms within the TNF promoter gene are associated with susceptibility to coal workers' pneumoconiosis (CWP), the DNA of 78 coal miners was typed for G-to-A transitions at positions −238 and −308. Our results show that frequency of A⁻³⁰⁸ genotype (T2) is significantly overpresented in coal miners with CWP (50%), as compared with miners without CWP (25%) and controls (29%). After correction for cumulative dust exposure and smoking, the A⁻³⁰⁸ transition genotype is still associated with the presence of CWP (OR = 3.0, 95%CI = 1.0–9.0). Both A⁻²³⁸ and A⁻³⁰⁸ transition genotypes were related to TNF release from endotoxin-stimulated blood monocytes; only the A⁻²³⁸ transition and not the A⁻³⁰⁸ transition was associated to coal dust-induced TNF release. In summary, this study shows that the A⁻³⁰⁸ transition is related to CWP, but this relation is not paralleled by a different TNF release in this genotype. A larger number of patients coupled to frequent TNF release are required to evaluate genotype screening to estimate individual health risks for effects of coal mine dust exposure. Am. J. Ind. Med. 34:318–324, 1998. © 1998 Wiley-Liss, Inc.     

白细胞介素-6基因多态性与尘肺的相关性

目的 研究白细胞介素-6（IL-6）（-634C/G）基因多态性与尘肺的关系.方法 选择确诊的104例Ⅰ期男性矽肺患者66例（矽肺组）、煤工尘肺患者38例（煤工尘肺组）为研究对象,以接触同性质粉尘、非尘肺的122名男性接触矽尘工人77例（矽尘组）、接触煤尘工人45例（煤尘组）为对照;采集外周静脉血,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测IL-6（-634C/G）基因多态性.结果 IL-6（-634C/G）基因型（CC、CG、GG）在矽肺组、矽尘组、煤工尘肺组和煤尘组分布频率分别为66.7%、19.7%、13.6%,42.9%、42.9%、14.2%,73.7%、18.4%、7.9%和51.1%、35.6%、13.3%.成组分析和1：1配对分析中均发现IL-6（-634C/G）基因型分布频率在矽肺组和矽尘组间差异有统计学意义（P＜0.05）.结论 IL-6（-634 C/G）基因多态性与矽肺发病相关.     

Neopterin as a marker for immune system activation in coal workers' pneumoconiosis

Coal workers' pneumoconiosis (CWP) is an occupational pulmonary disease that occurs by chronic inhalation of coal dust. Coal workers' pneumoconiosis is divided into two categories depending on the extent of the disease as simple pneumoconiosis (SP) and progressive massive fibrosis (PMF). Development of CWP is associated with the activation of the immune system. Neopterin is a predictive biochemical marker of cell-mediated immune activation and elevated levels of neopterin are detected in body fluids of patients with immune-related diseases. The present study was aimed to investigate whether increased serum, urine and bronchoalveolar lavage (BAL) fluid levels of neopterin is associated with the development and/or severity of CWP. Mean serum neopterin levels in SP and PMF patients (10.72 +/- 0.98 nmol/L; 14.08 +/- 3.86 nmol/L, respectively) were significantly higher than those of control group (5.30 +/- 0.47 nmol/L) (P < 0.05). Although urinary neopterin levels were also increased in SP and PMF patients (235.17 +/- 7.40 micromol/mol creatinine; 256.05 +/- 9.43 micromol/mol creatinine, respectively) as compared with the control group (140.00 +/- 5.43 micromol/mol creatinine) (P < 0.01), they were within the normal concentration range. No significant difference was observed between serum and urinary neopterin levels of SP and PMF patients. A correlation was observed between serum and urinary neopterin levels of all subjects (r = 0.525, P < 0.01). Bronchoalveolar lavage fluid neopterin levels were significantly higher in patients with SP and PMF (22.67 +/- 2.9 nmol/L; 41.67 +/- 8.68 nmol/L, respectively) compared with control subjects (6.264 +/- 1.74 nmol/L) (P < 0.05, P < 0.01, respectively). The levels of neopterin in BAL fluid were also significantly higher in patients with PMF than in those with SP (P < 0.05). These findings indicate that elevated serum and BAL levels of neopterin may be considered as a suitable biomarker for the assessment of CWP.     

肿瘤坏死因子-α及其Ⅱ型受体基因多态性与煤工尘肺

目的　探讨肿瘤坏死因子 α(TNF α)及其Ⅱ型受体 (TNFRⅡ )基因多态性在煤工尘肺发病遗传易感性中的作用及其与煤工尘肺纤维化程度的联系。方法　选择 2 34例汉族煤工尘肺患者和4 4 0例煤尘接触者为研究对象 ,拍摄高仟伏X射线后前位胸片 ,按尘肺病诊断标准进行诊断和分期 ;采集研究对象的外周静脉血 ,应用多聚酶链反应 -限制片段长度多态性 (PCR RFLP)技术检测其TNF α及TNFRⅡ基因多态性。结果　TNF α - 30 8位点G A A A基因型和TNFRⅡ 196位点T G G G基因型分布频率在成组或 1∶1配对分析中 ,煤工尘肺患者和煤尘接触者两组间差异均无显著性 (P >0 .0 5 )。G A A A基因型频率在Ⅲ期煤工尘肺患者中为 2 0 .0 0 % ,高于煤尘接触者 (10 .91% )、Ⅰ期(10 .34% )和Ⅱ期煤工尘肺患者 (7.5 0 % ) ;1∶1配对后 ,G A A A基因型携带者发展成Ⅲ期煤工尘肺的危险性是G G基因型的 3倍 (95 %CI:0 .35～ 2 5 .84 )。结论　TNF α和TNFRⅡ基因多态性在汉族煤工尘肺发病的遗传易感性中不起主要作用。TNF α基因多态性可能与煤工尘肺纤维化严重程度相关。     

煤工尘肺患者血清TNF-α水平及意义

  目的  通过检测煤工尘肺患者血清中肿瘤坏死因子-α（tumor necrosis factor alpha,TNF-α）水平,为了解其在煤工尘肺发展过程中的变化动态提供实验依据。
  方法  利用便利抽样方法,选取北京某医院117例煤工尘肺患者,调查相关信息,采用酶联免疫法检测患者外周血TNF-α水平。
  结果  不同工龄、不同期别和不同吸烟状况下煤工尘肺患者之间的血清TNF-α水平差异均无统计学意义（P > 0.05）;但工龄、尘肺病诊断年限与TNF-α水平均存在一定程度的相关关系（r_s = 0.603、0.186,P < 0.05）;随着诊断年限的增长,TNF-α水平呈现升高的趋势,≤10年、11 ~ 20年和> 20年患者TNF-α浓度分别为（0.99 ±0.39）pg/mL、（1.20 ±0.47）pg/mL和（1.21 ±0.44）pg/mL,差异有统计学意义（P < 0.05）。
  结论  血清中TNF-α水平可能与煤工尘肺的发展有一定关系,其具体机制有待进一步研究探讨。
     

白细胞介素-1基因多态性与尘肺易感性的关系

目的 探讨白细胞介素-1（IL-1）基因多态性与尘肺易感性的关系.方法 以80例Ⅰ期矽肺和45例Ⅰ期煤工尘肺为病例,以与病例年龄相差小于5岁、同性别、同民族、同一工作地点、开始接尘时间和累积接尘工龄相差不超过2年的非尘肺接尘工人为对照,进行1：1配对.采集静脉血,用酚-氯仿法抽提DNA,采用聚合酶链反应限制性片段长度多态性（PCR-RFLP）和PCR方法检测IL-1α（-889）、IL-1β（-511）、IL-1 Ra（＋2018）和IL-1Ra数目可变的串联重复序列4个基因位点的基因型,并进行单因素、多因素分析.结果 两组IL-1α（-889）1/2＋2/2基因型的携带率的差异有统计学意义（P＜0.01）,病例组与对照组IL-1α（-889）等位基因2的频率分别为57.6%和40.8%,差异有统计学意义（P＜0.01）,多因素分析表明,IL-1α（-889）突变基因型及等位基因2为尘肺的危险因素.病例组与对照组之间IL-1β（-511）1/2＋2/2基因型、IL-1 Ra（＋2018）1/2＋2/2基因型和IL-1Ra VNTR1/2＋2/2基因型携带率的差异均无统计学意义（P＞0.05）,病例组与对照组IL-1β（-511）、IL-1 Ra（＋2018）和IL-1 Ra VNTR等位基因2的频率差异无统计学意义（P＞0.05）.矽肺组和煤工尘肺组间4个等位基因及基因型分布频率差异均无统计学意义（P＞0.05）.结论 IL-1α（-889）基因多态性与尘肺患病有关,携带IL-1α（-889）等位基因2的接尘者患尘肺的危险性增加,未发现IL-1β（-511）、IL-1Ra（＋2018）及IL-1 Ra VNTR基因多态性与尘肺发病有关联.     

IL-12B＋1188A／C基因多态性与宁夏汉族煤工尘肺易感性研究

[目的]探讨白介素-12B（interleukin-12B,IL-12B）基因3＇UTR区1188A／C位点多态性与宁夏汉族煤工尘肺（coal worker’s pneumoconiosis,CWP）易感性的关系。[方法]采用聚合酶链反应-限制片段长度多态性（PCR—RFLP）法对120例CWP患者和120例煤尘接触组IL-12B基因1188A／C位点多态性进行分型,对等位基因及基因型分布进行统计学分析。[结果]煤工尘肺组与煤尘接触组在接尘工龄、工种构成、吸烟烟龄差异无统计学意义（P〉0．05）.对年龄进行标化后,分析发现IL-12B 1188A／C位点在煤工尘肺组和煤尘接触组中检出三种基因型爿爿、AC、CC型,这三种基因型在尘肺组和接触组间分布差异无统计学意义（P〉0．05）;等位基因C在煤工尘肺组和煤尘接触组中所占比例分别为45．8％和36．7％,差异有统计学意义（P〈0．05）,在接尘工龄、工种和是否吸烟中的分布无差异（P〉0．05）.[结论]IL-12B 1188A／C位点C等位基因可能是宁夏汉族煤工尘肺的易感基因之一。     

转化生长因子-β1基因509C/T多态性在宁夏煤工尘肺人群中的分布

[目的]探讨转化生长因子-β1（TGF-β1）基因509C/T多态性在宁夏汉族煤工尘肺（coal worker’s pneumoconiosis,CWP）人群中的分布情况。[方法]从宁夏某煤业集团所属煤矿已确诊的病例中随机抽取110名煤工尘肺病例（煤工尘肺组）、110名煤尘接触者（煤尘接触组）和110名当地不接尘的正常居民（非煤尘接触组）为研究对象,采集静脉血,使用聚合酶链反应-限制片段长度多态性（PCR-RFLP）分析TGF-β1基因509CT位点多态性。[结果]煤工尘肺组、煤尘接触组及非煤尘接触组平均年龄分别为（48.30±13.16）岁、（43.86±4.20）岁、（41.73±5.45）岁。煤工尘肺组和煤尘接触组工龄分别为（17.40±7.84）年和（16.95±6.10）年。工种构成：主掘进工在煤工尘肺组和煤尘接触组中分别占48.2%和49.1%。煤工尘肺组和煤尘接触组及非煤尘接触组中吸烟烟龄分别为（10.48±10.12）年、（11.34±10.48）年、（12.65±11.53）年;接尘工龄、工种构成、吸烟烟龄均无差别,均P〉0.05。TGF-β1基因509C/T位点多态性在煤工尘肺组、煤尘接触组及非煤尘接触组中所占比例分别为51.8%、30.9%、25.5%;等位基因频率T在煤工尘肺组、煤尘接触组及非煤尘接触组中所占比例分别为40.90%、23.20%、19.10%;煤工尘肺组与煤尘接触组比较,TGF-β1基因中CT基因型差异有统计学意义（P〈0.01）。煤工尘肺组不同期别人群的等位基因频率差异有统计学意义（P〈0.01）。[结论]TGF-β1-509C/T位点多态性在宁夏地区煤工尘肺者中的分布可能不同。     

Genetic polymorphisms of MnSOD, GSTM1, GSTT1, and OGG1 in coal workers' pneumoconiosis

Little is known about the genetic susceptibility to coal workers' pneumoconiosis (CWP). We investigated the association between genetic polymorphisms of MnSOD, GSTM1, GSTT1, or OGG1 and susceptibility to CWP. The study population was composed of 259 Chinese retired coal miners who had similar dust exposure histories. Of these, there were 99 cases with International Labor Organization chest radiologic criteria for CWP and 160 controls (with no radiologic criteria for CWP). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Polymerase chain reaction-based techniques evaluated the genotypes of all study subjects. There were no differences in genotype frequency of MnSOD, GSTM1, GSTT1, and OGG1 between miners with CWP and miners without CWP, by logistic regression analysis. Cumulative dust exposures, but not genetic polymorphisms, were associated significantly with the presence of CWP. This study illustrates the complexity of factors that may contribute to the development of CWP.     

煤工尘肺患者肺通气功能障碍的影响因素

目的分析煤工尘肺(CWP)患者肺功能障碍的可能影响因素。方法采用病例-对照研究,分别选择141名CWP患者为病例组,200名非CWP的接尘矿工为接尘组,75名非从事接尘作业的健康者为对照组,均为男性。对研究对象调查接尘工种、接尘工龄、肺部疾病、吸烟及职业卫生防护情况等,并测定肺通气功能,根据对照人群特征建立相应肺功能指标的预计回归方程计算预计值,以各指标的实测值和预计值之比对肺功能障碍进行分型,采用非条件Logistic回归模型对影响因素进行分析。结果病例组及接尘组FVC、FEV_(1.0)实测值及FVC、FEV_(1.0)实测值与其预测值的比值均明显低于对照组,差异有统计学意义(P<0.05);随煤工尘肺分级增加,限制性和混合性通气功能障碍发生率明显增高(x~2=67.46,51.19,P<0.05);佩戴口罩情况、CWP分期、吸烟程度、接尘工龄等指标均被选入非条件Logistic回归模型。结论影响煤工尘肺患者肺功能障碍的因素可能有CWP晋级、是否坚持佩戴口罩、吸烟、接尘工龄等。     

Pneumoconiosis and advanced occupational lung disease among surface coal miners--16 states, 2010-2011

Coal workers' pneumoconiosis (CWP) is a chronic occupational lung disease caused by long-term inhalation of dust, which triggers inflammation of the alveoli, eventually resulting in irreversible lung damage. CWP ranges in severity from simple to advanced; the most severe form is progressive massive fibrosis (PMF). Advanced CWP is debilitating and often fatal. To prevent CWP, the Coal Mine Health and Safety Act of 1969 established the current federal exposure limit for respirable dust in underground and surface coal mines. The Act also established a surveillance system for assessing prevalence of pneumoconiosis among underground coal miners, but this surveillance does not extend to surface coal miners. With enforcement of the exposure limit, the prevalence of CWP among underground coal miners declined from 11.2% during 1970-1974 to 2.0% during 1995-1999, before increasing unexpectedly in the last decade, particularly in Central Appalachia. Exposure to respirable dust is thought to be less in surface than underground coal miners. Although they comprise 48% of the coal mining workforce, surface coal miners have not been studied since 2002. To assess the prevalence, severity, and geographic distribution of pneumoconiosis among current surface coal miners, CDC obtained chest radiographs of 2,328 miners during 2010-2011 through the Coal Workers' Health Surveillance Program of the National Institute for Occupational Safety and Health (NIOSH). Forty-six (2.0%) of 2,257 miners with >1 year of surface mining experience had CWP, including 37 who had never worked underground. Twelve (0.5%) had PMF, including nine who had never worked underground. A high proportion of the radiographs suggested silicosis, a disease caused by inhalation of crystalline silica. Surface coal mine operators should monitor worker exposures closely to ensure that both respirable dust and silica are below recommended levels to prevent CWP. Clinicians should be aware of the risk for advanced pneumoconiosis among surface coal miners, in addition to underground coal miners, to facilitate prompt disease identification and intervention.     

Evaluation of serum type III procollagen peptide as an exposure marker in retired coal workers

Serum type III procollagen peptide (PIIIP), a degradation product of the type III collagen precursor, has been put forward as an exposure marker for mineral dust. We evaluated PIIIP levels as a marker of exposure to and effects of coal dust in retired coal miners (n = 104). To this end: (a) the individual cumulative dust exposure was calculated from job-exposure matrices, and (b) in addition to routine chest radiography (CR) of all miners according to the criteria of the International Labour Organisation (ILO), a subgroup (n = 46) was screened by high-resolution computed tomography (HRCT). Profusion score (CR and HRCT) tended to increase with cumulative dust exposure, even in the absence of CR evidence for pneumoconiosis (i.e. CR , 0/1, n = 35). In contrast to our previous findings in active miners, PIIIP levels were not increased in miners as compared with non-dust-exposed controls (n = 29), and no differences were observed between miners without (ILO = 0/0) and miners with coal workers' pneumoconiosis (CWP; ILO 0/1). No trend in PIIIP versus pneumoconiosis stage was present, either by CR or by the more sensitive HRCT score. PIIIP was also unrelated to any lung function parameter (FEV₁, FVC, impedance, diffusion capacity). Age, medication, medical history and smoking habits had no significant effect on PIIIP levels. In the miners with CWP (i.e. ILO > 0/0, n = 28) a significant negative correlation was present between PIIIP values and (log) cumulative dust exposure. This decrease in serum PIIIP levels with increasing cumulative exposure may be due to chronic adaptive changes in type III collagen deposition and/or breakdown. Other relations between exposure and PIIIP were not observed. In conclusion, the present findings do not support the use of serum type III procollagen peptide as a marker of exposure to and (early) interstitial or respiratory effects of coal dust.     

肿瘤坏死因子α-308位点基因多态性与胃癌易感性的Meta分析

目的 评价肿瘤坏死因子α(TNF-α)基因启动子区-308位点基因多态性与胃癌易感性.方法 检索PubMed、EMBASE数据库、Cochrane图书馆(1966年至2009年7月)及万方、中国生物医学文献数据库(1979年至2009年7月)文献,收集TNF-α-308位点基因多态性与胃癌易感性的病例对照研究,共检索到39篇相关文献,26篇纳入研究.应用RevMan 4.2对各研究结果进行异质性检验和效应值合并.结果 26篇纳入本研究的文献中,共计有5225例胃癌患者和8473例(名)对照人群.总研究人群TNF-α-308位点基因G:A的OR=0.85(95%CI:0.76～0.96,P=0.01),AA:GG基因型OR值为1.19(95%CI:1.01～1.39,P=0.03).分层分析显示,东方人种G:A的OR=0.97(95%CI:0.75～1.26,P=0.84),西方人种G:A的OR=0.79(95%CI:0.70～0.89,P＜0.01),AA:GG基因型OR值为1.26(95%CI:1.04～1.52,P=0.02).非贲门胃癌患者G:A的OR=0.90(95%CI:0.79～1.02,P=0.10),幽门螺杆菌阳性胃癌患者G:A的OR=1.08(95%CI:0.62～1.88.P=0.79).结论 西方人种TNF-α-308位点A等位基因及从基因型与胃癌遗传易感性相关,携带A等位基因患者增加罹患胃癌的风险.     

Does Coal Workers Pneumoconiosis Predict to Lung Cancer? Some Evidence from a Case-Control Study

Previous reports on the relationship between coal workers' pneumoconiosis(CWP) and lung cancer mortality have shown widely differingresults. Concern has centred especially around whether or notthere is an aggregation of complicated CWP, or Progressive MassiveFibrosis (PMF), with lung cancer. This paper evaluates, amongUS coal miners, the CWP-lung cancer relationship by computingthe lung cancer mortality risk of simple and complicated CWPas well as the interactions with cigarette smoking and ventilatoryfunction. Two case-control studies based on 317 white male lungcancer mortality cases are presented. A one-to-one matched-casedesign allows examination of the lung cancer mortality riskof CWP and cigarette smoking. A two-to-one matched-case designcontrols on smoking status. Based upon these data, no evidenceof a CWP-lung cancer risk was found, although the expected increasedrisk for lung cancer mortality in cigarette smokers was observed.No relationship was found between PMF and lung cancer mortalityrisk. Finally, no evidence was found of interaction effectsbetween cigarette smoking or ventilatory function and CWP aspredictors of lung cancer mortality risk. Requests for reprints should be addressed to: R. G. Ames, Appalachian Laboratory, US National Institute for Occupational Safety and Health, 944 Chestnut Ridge Road, Morgantown, West Virginia 26505, USA.     

SMAD4基因多态性与煤工尘肺易感性

目的 探讨SMAD4基因单核苷酸多态性(SNPs)与煤工尘肺易感性的关系.方法 采用病例-对照的研究方法,选择438例煤工尘肺患者为病例组,448例同单位、同工种、工龄接近、无尘肺的煤尘接触者为对照组,进行统一的问卷调查;拍摄高仟伏X线后前位胸片;采集外周静脉血,酚-氯仿法提取DNA;根据中国人群HapMap database数据库查找SNP位点,多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测SMAD4 6个SNPs位点的基因型.结果 6个SNPs位点的基因型分布频率中,仅SMAD4(rs10502913)病例组和对照组各基因型分布频率比较,差异有统计学意义(x2=6.512,P=0.038).携带SMAD4(rs10502913)AA基因型者发生煤工尘肺的危险性明显增高(调整后OR=1.63,95%CI=1.00～2.69,P=0.05);以是否吸烟为分层分析显示,携带SMAD4(rs10502913)AG基因型的不吸烟者发生煤工尘肺的危险性降低(调整后OR=0.54,95%CI=0.37～0.78,P＜0.01),而携带SMAD4(rs10502913)AG、AA基因型的吸烟者发生煤工尘肺危险性均增高(AG调整后OR=1.59,95%CI=1.01～2.50,P＜0.05;AA调整后OR=2.28,95%CI=1.09～4.80,P＜0.05);以煤工尘肺分期为分层分析显示,Ⅰ期尘肺组携带SMAD4(rs10502913)AA基因型者发生尘肺的危险性是携带GG型的2.42倍(调整后OR=2.42,95%CI=1.41～4.14,P＜0.01).携带SMAD4(rs9304407)GG基因型者煤工尘肺患病危险性与CC基因型比较明显降低(调整后OR=0.65,95%CI=0.43～0.98,P＜0.05);以是否吸烟为分层分析显示,不吸烟携带SMAD4(rs9304407)GC、GG基因型者发生煤工尘肺危险性明显降低(GC基因型调整后OR=0.60,95%CI=0.36～1.00,P＜0.05;GG基因型调整后OR=0.43,95%CI=0.25～0.74,P＜0.01).结论 SMAD4(rs10502913)位点AA基因型增加了煤工尘肺的危险性,SMAD4(rs9304407)位点GG基因型可能在尘肺的发生发展中起保护性作用.     

煤工尘肺患者血清中基质金属蛋白酶-9及其抑制因子水平的变化

目的 探讨煤工尘肺患者血清中基质金属蛋白酶(MMP-9)及基质金属蛋白酶抑制剂(TIMP-9)水平的变化及意义.方法 采用双抗体夹心ELISA法检测188例煤工尘肺(煤肺组53例,煤矽肺组67例,矽肺组68例)、57例0期(0~+期组)、64例接尘对照组和50例健康对照组血清中MMP-9及TIMP-9含量;分析血清中MMP-9和TIMP-9水平在各煤工尘肺组及各对照组间的变化,以及二者的相关性;并根据煤工尘肺期别、是否有并发症以及接尘年限等因素进行分析.结果 煤肺组血清中MMP-9水平为17.16 ng/ml、煤矽肺组为15.14ng/ml,矽肺组为17.50 ng/ml,与健康对照组比较,差异均有统计学意义(P<0.05)与接尘对照组、0~+组比较,均呈降低趋势,其中矽肺组及煤矽肺组差异有统计学意义(P<0.05).3组煤工尘肺患者血清中MMP-9水平比较,差异无统计学意义(P>0.05);煤肺组、煤矽肺组和矽肺组血清中TIMP-9水平分别为(330.00±108.42),(312.044±120.09),(366.81±135.50)ng/ml,均低于健康对照组,其中矽肺组和煤肺组血清中TIMP-9水平较接尘对照组、1~+组明显增高,差异有统计学意义(P<0.05),3组煤工尘肺组间比较,矽肺组血清中TIMP-9水平较煤矽肺组升高,差异有统计学意义(P<0.05).3组煤工尘肺患者血清中MMP-9和TIMP-9水平按不同的疾病分期、是否有并发症以及接尘年限进行分析,差异均无统计学意义(P>0.05);矽肺组血清中TIMP-9水平与年龄呈正相关(r=0.249,P<0.05),血清中MMP-9和TIMP-9水平在接尘对照组中呈正相关(r=0.294,P<0.05),其他组中未发现相关性.结论 血清中MMP-9与TIMP-9水平变化与粉尘对机体的损害程度有关,MMP-9与TIMP-9共同参与了煤工尘肺的病理生理过程;动态观察0~+期及健康煤矿工人血清中MMP-9和TIMP-9水平,可为煤工尘肺的预防及早期诊断提供参考.     

CT和高分辨CT对煤工尘肺小阴影和阴影融合及肺气肿诊断的价值

目的 探讨CT和高分辨CT(HRCT)早期检测煤工尘肺小阴影、阴影融合与肺气肿的敏感性和准确性.方法 77例煤工尘肺患者、36例无尘肺煤工和37例健康非煤工接受多层螺旋CT机无间隔胸部容积扫描及HRCT扫描,对所获得的CT图像进行煤工尘肺小阴影密集度分级、平均肺密度值和肺气肿指数测定,并与其X线胸片诊断结果对照.结果 对77例煤工尘肺患者CT和HRCT诊断的尘肺小阴影密集度分级与X线胸片尘肺分期一致性较好(Kappa=0.771,P＜0.01).CT和HRCT诊断尘肺的敏感性达到98.70％,在X线胸片确诊的77例煤工尘肺患者中,CT和HRCT评估76例为煤工尘肺,可疑1例.CT和HRCT从36例X线胸片无尘肺煤工中检出8例(22.22％)达到小阴影密集度1级;从73例Ⅰ～Ⅱ期煤工尘肺患者中,检出26例(35.62％)阴影密集度≥3级,其中3级密集度阴影20例,4级密集度阴影6例;对4例X线胸片Ⅲ期煤工尘肺患者,CT和HRCT与X线胸片诊断结果相同.从113例煤工中,X线胸片检出肺气肿7例(6.19％),CT检出36例(31.86％).CT尘肺小阴影密集度1～2级组的CT平均肺密度值最高,明显高于健康对照组、无尘肺组和小阴影密集度4级组,差异有统计学意义(F1=-45.73、F2=-23.00和F3=57.72,P＜0.01或P＜0.05).结论 从多层螺旋CT获得的CT和HRCT影像,与X线胸片比较,对煤工尘肺小阴影、阴影融合与肺气肿识别的敏感性和准确性均较高,可为煤工尘肺及其并发症的早期诊断提供更先进的手段.     

白细胞介素-8基因多态性与矽肺易感性研究

目的 探讨白细胞介素(IL)-8基因多态性与矽肺易感性的关系.方法 选择确诊的101例矽肺患者为病例组,以接触同性质粉尘、首次诊断年龄相近的非矽肺的接尘工人为对照(121例).采集外周静脉血,盐析法提取DNA,应用聚合酶链-限制性片段长度多态性(PCR-RFLP)技术检测IL-8(Met31Arg、781C/T、-251A/T、RA+860)4个位点的基因型和等位基因频率并进行分析.结果 两组对象的首次诊断年龄、累积接尘工龄、吸烟率的差异均无统计学意义(P＞0.10).病例组IL-8(Met31Arg)GT基因型的分布频率为12.87%,对照组为2.48%,差异有统计学意义(P＜0.05),病例组和对照组携带等位基因G的频率分别为6.44%和2.07%,差异有统计学意义(P＜0.05).病例组IL-8(-251A/T)从基因型的分布频率为9.90%,对照组为25.62%,差异有统计学意义(P＜0.05).病例组IL-8(781C/T)基因型CC、CT、TT的分布频率分别为38.61%、40.59%、20.79%,与对照组(46.28%、40.50%、13.22%)相比,差异无统计学意义(P＞0.05).病例组IL-8(RA+860)基因型GG、GC、CC的分布频率分别为75.25%、21.78%、2.97%,与对照组(80.17%、14.88%、4.96%)相比,差异无统计学意义(P＞0.05).结论 IL-8的Met31Arg位点和一251MT位点的基因多态性与矽肺易感性有关,携带IL-8(Met31Arg)GT基因型的接尘工人患矽肺的危险性增加;携带IL-8(-251)从基因型的接尘工人患矽肺的危险性降低.未发现IL-8(781C/T和RA+860)位点的基因多态性与矽肺易感性有关.

Abstract：

Objective To explore the relationship between the polymorphisms of interleukin-8(IL-8)and the silicosis susceptibility. Methods The case group consisted of 101 male patients with stage I silicosis diagnosed by the Pneumoconiosis Diagnosis Expert Panel according to the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70-2009). The control group consisted of 121 workers without silicosis exposed to same dusts. The cases and the controls had the same dust exposure history. The peripheral venous blood was drawn from each subject. DNA was extracted from leucocytes by the salting method. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) techniques and PCR were used to examine polymorphism of IL-8(Met31Arg, 781C/T,-251A/T and RA+860). Results There were no the differences of age, cumulative exposure time and smoking between the cases and the controls (P＞0.05). The frequencies of IL-8 (Met31Arg) GT genotypes in cases and controls were 12.87% and 2.48%, respectively, there was significant difference (P＜0.05).The frequencies of allele G in cases and controls were 6.44% and 2.07%, respectively, there was significant difference (P＜0.05). The frequencies of IL-8 (-251A/T) AA genotypes in cases and controls were 9.90% and 25.64%, respectively, there was significant difference (P＜0.05). The frequencies of IL-8 (781C/T) CC, CT, TT genotypes in cases and controls were 38.61%,40.59%,20.79% and 46.28%,40.50%, 13.22%, respectively, there zwas no significant difference (P＞0.05). The frequencies of IL-8 (RA+860) GG, GC and CC genotypes in cases and controls were 75.25%, 21.78%, 2.97%, 80.17%, 14.88%, 4.96%, respectively, there was no significant difference (P＞0.05). Conclusions IL-8 (Met31 Arg and -251A/T) genetic polymorphisms might play a role in the development of silicosis. The risk of pneumoconiosis in workers carrying (Met31 Arg) genotype GT is likely to increase.The risk of pneumoconiosis in workers carrying IL-8 (-251A/T) AA genotype is likely to decrease. The relationship between IL-8 781C/T and RA+860 genes polymorphisms and silicosis is not found.