中国南方汉族人β-defensin-1基因多态性与慢性阻塞性肺疾病易感性的关系

目的　探讨中国南方汉族人 β- defensin- 1基因多态性与慢性阻塞性肺疾病 (COPD)易感性的关系。方法　采用限制性片段长度多态性 (RFLP)技术检测 β defensin -1外显子 2基因型在 12 0例COPD吸烟患者和10 8例非COPD吸烟者中的频率。结果　COPD组同源野生型 (G/G)、杂合型 (G/A)和同源突变型 (A/A)频率分别为 82 .5 0 %、10 .83%和 6 .6 7% ,非COPD组的频率分别为 95 .37%、3.70 %和 0 .93% ,两组基因频率分布的差异有显著性 (P <0 .0 1)。两组等位基因的分布差异也有显著性 (等位基因G频率分别为 87.92 %∶97.2 2 % ;等位基因A频率分别为 12 .0 8%∶2 .78% ;P <0 .0 1) ;G→A的突变率随COPD病情的严重度增加而上升。结论　β defensin 1基因外显子 2的 16 5 4位多态性与中国南方汉族人群COPD易感性可能有关 ,而且可能还影响COPD的进展。     

CC16基因38A/G多态性与慢性阻塞性肺疾病的相关性研究

目的：探讨C lara细胞分泌蛋白（CC16）基因38 A/G多态性与内蒙古地区汉族人群慢性阻塞性肺疾病（COPD）的相关性。方法：采用病例-对照研究方法和聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术,检测和分析COPD组（70例）与正常对照组（70例）CC16基因第1外显子38位点的各种基因型和等位基因频率。结果：COPD与对照组CC16基因第1外显子38位点的基因型频率和等位基因频率差异无统计学意义（P〉0.05）;COPD组与对照组中吸烟者CC16基因型频率比较差异有统计学意义（χ2=6.853,P〈0.05）,COPD组吸烟者AA基因型频率较不吸烟者明显增多（32.7%与8.0%）,AA型吸烟者患COPD的风险是非AA型吸烟者的4.082倍。结论：吸烟与CC16基因第1外显子38 A/G多态性在COPD的发病中存在交互作用,CC16基因可能是微效基因,其作用的发挥与吸烟密切相关。     

Detection of p53 gene mutations in sputum samples and their implications in th e early diagnosis of lung cancer in suspicious patients

目的　评价痰标本检测p5 3基因点突变方法及其作为肺癌早期临床诊断监测指标的真实性和可靠性。方法　用PCR SSCP 银染法检测 5 4例原发性肺癌患者和 114例良性肺疾患者痰标本中p5 3基因第 5 - 8外显子的点突变 ,同时进行痰涂片细胞学检查。结果　p5 3突变在肺癌组检出率为 5 5 5 6 % (30 /5 4 ) ,非肺癌组检出率为 1 75 % (2 /114) (P <0 0 0 1)。痰标本检测p5 3基因突变作为肺癌临床诊断监测指标的灵敏度 5 5 5 6 %、特异度 98 2 5 %、阳性似然比 31 75。肺癌组p5 3阳性检出率 5 5 5 6 % (30 /5 4 )与痰涂片瘤细胞阳性检出率 35 19% (19/5 4 )比较 :差异性有显著意义 (P <0 0 5 ) ,关联性有极显著意义 (P <0 0 1)。肺癌组p5 3检出率与性别、吸烟指数、病理分型、疾病分期均无明显关系 ,但与年龄有密切关系 ,高龄患者 ( 6 0岁 )检出率高 (P =0 0 2 )。非肺癌组一例慢性阻塞性肺病 (COPD)患者检测到E5突变 ,随访四年 ,确诊为肺鳞癌。结论　PCR SSCP 银染法检测痰标本p5 3突变可以在可疑肺癌患者 (如吸烟者合并慢性肺疾患 )中作为一项随访监测指标 ,将有助于肺癌早期临床诊断。     

微粒体环氧化物水解酶基因多态性与慢性阻塞性肺疾病的关系

目的 明确微粒体环氧化物水解酶(mEH)基因多态性与中国人慢性阻塞性肺疾病(COPD)易感性的关系。方法 用聚合酶链反应—限制性片段长度多态性(PCR—RFLP)分析的方法检测100对年龄、性别匹配的COPD患者和健康对照者mEH外显子3(Tyr113→His)、外显子4(His139→Arg)基因多态性。结果 (1)COPD组有42例(42％),对照组有32人(32％)为mEH外显子3的His139突变杂合子(P=0．015),经年龄、性别、体块指数和吸烟年支数调整后的OR值为2.96(95％CI为1．24～7．09);(2)极慢代谢活性的mEH基因型对应其他代谢活性基因型在病例组和对照组间未发现明显差别;(3)将病例组分为不吸烟者和吸烟者(包括目前仍吸烟者和戒烟者)两组,极慢代谢活性的mEH基因型对应其他代谢活性基因型在不吸烟者OR值均大于1.00,而在吸烟者中均小于1．00。结论 (1)mEH外显子3的His113突变杂合子与中国COPD易感性有关;(2)COPD患者mEH基因型与吸烟之间可能存在交互作用。     

扩张型心肌病与δ-肌聚糖基因突变

目的 :探讨中国人扩张型心肌病患者中δ-肌聚糖 (δ- sarcoglycan,SGCD)基因的突变情况。方法 :通过聚合酶链反应 -单链构象多态性分析 ,结合 DNA测序 ,对 60例扩张型心肌病患者和 60例对照 SGCD基因的所有 9个外显子进行分析。结果 :该基因外显子 9m发现 3种类型的单链构象多态性图谱 ;DNA测序证实其中一种为正常野生型 ,另外两种为832 G/A和 848A/G突变杂合子。 832 G/A突变 ( 2 78Ala→ Thr)仅在对照组检出 1例 ,对照组 A等位基因频率 0 .0 0 8;848A/G突变 ( 2 83Gln→ Arg)共检出 5例 ,G等位基因频率在扩张型心肌病组和对照组中差异无显著性 ( P>0 .2 5 ) ,对照组 G等位基因频率 0 .0 33。结论 :发现 SGCD基因 2个新的突变位点 ;未能证实这 2个位点的突变与扩张型心肌病相关     

慢性阻塞性肺疾病患者血浆可溶性细胞间粘附分子-1含量变化的研究

目的　探讨可溶性细胞间粘附分子 1 (sICAM 1 )在慢性阻塞性肺疾病 (COPD)中的作用。方法　COPD患者 35例 ,分为缓解期组 1 5例 ,加重期组 2 0例 ;健康体检者 1 8例作正常对照组。用ELISA法测定各组血浆中sICAM 1的含量 ,肺功能仪测量 1s用力呼气容积占用力肺活量的百分比 (FEV1 /FVC) ,并将两者作统计学相关分析。结果　正常对照组、COPD缓解期组和加重期组的血浆sICAM 1含量分别为 (2 1 .40± 3 .596) μg/L、(30 .59± 4 .1 55)μg/L和 (38.40± 3 .943) μg/L ,3组组间差异均有统计学意义 (P <0 .0 1 ) ;FEV1 /FVC分别为 (97.4± 8.0 5) %、(53 .3±7.85) %和 (48.7± 3 .72 ) % ,3组组间差异亦有统计学意义 (P <0 .0 5) ;COPD缓解期组血浆sICAM 1与FEV1 /FVC呈负相关 (r =- 0 .738,P <0 .0 0 2 ) ,加重期组亦存在负相关关系 (r =- 0 .864 ,P <0 .0 0 1 )。结论　ICAM 1参与COPD的发病过程 ,血浆sICAM 1含量可作为评价COPD病情严重程度及预后的指标     

心钠素基因T 2238C多态性与2型糖尿病肾病易感性的相关性研究

目的　观察心钠素 (ANF)基因第 3外显子上ScaI酶切位点T 2 2 38C多态性与 2型糖尿病肾病(DN)易感性的关系。方法　选择 96例无亲缘关系中国北方地区 2型糖尿病患者为研究组 ,其中正常清蛋白尿 (NA) 4 3例 ,糖尿病肾病组 5 3例。 4 0例无亲缘关系北方中国人为健康对照组 ,通过聚合酶链反应 -限制性内切酶长度多态性技术 (PCR -RFLP)检测ANF基因T 2 2 38C多态性。结果　ANF基因TC基因型分布在NA组高于DN组 (χ2 =5 349,P =0 0 2 1 ) ,等位基因C频率分布在NA组高于DN组 (χ2 =4 76 1 ,P <0 0 5 )。结论　心钠素 (ANF)基因第 3外显子上ScaI酶切位点 ,T 2 2 38C多态性与 2型糖尿病肾病 (DN)易感性相关。C等位基因可能是 2型糖尿病肾病发生发展的保护性因素 ,可减少 2型糖尿病肾病发生的风险     

慢性阻塞性肺疾病合并糖尿病肺功能、血气变化及其意义

目的 :研究慢性阻塞性肺疾病 (COPD)合并糖尿病的肺功能及血气特点并探讨临床意义。方法 :根据是否合并糖尿病将 44例COPD稳定期病例分为COPD合并糖尿病组和单纯COPD组 ,分别测定 44例患者的肺功能指标(FEV1 %、FEV1 /FVC %、FEF2 5%、FEP50 %、TLCOSB %及TLCO/VA %)及血气指标 (PaO2 及PaCO2 mmHg)并对结果进行组间对比分析。结果 :两组比较FEV1 %、FEV1 %/FVC %、FEF2 5%及PaCO2 无显著性差异 ,COPD合并糖尿病组FEF50 %、TL COSB%、TLCO/VA %及PaO2 显著低于单纯COPD组 (P <0 0 5 ,P <0 0 1 )。结论 :COPD合并糖尿病时肺功能将进一步受损 ,其中以弥散功能损害更明显。     

eNOS基因第7外显子894G→T点突变与早期糖尿病肾病并高血压的关系

目的　探讨内皮细胞型一氧化氮合酶 (eNOS)基因第 7外显子 894位点多态性与糖尿病肾病并高血压的相关性。②方法　随机选择单纯 2型糖尿病病人 (2DM组 )、单纯糖尿病肾病病人 (DN组 )和糖尿病肾病并高血压病人 (DN +HP组 )为研究对象 ,应用PCR技术扩增目的片段 ,PCR产物以限制性内切酶BanⅡ进行酶切 ,2 0g/L的琼脂糖凝胶电泳分离。各组间等位基因频率及基因型频率的比较用卡方检验 ,危险因素分析用Logistic回归分析。③结果　DN病人组T等位基因和TG基因型频率显著高于单纯 2DM组 (χ2 =8.32～ 1 0 .2 3,P <0 .0 5 ) ,DN +HP组T等位基因及TG基因型频率与DN组比较差异无显著意义 (χ2 =0 .4 4、0 .6 1 ,P >0 .0 5 )。Lo gistic回归分析表明 ,体质量指数、HbA1c、TC、TG、eNOS基因第 7外显子 894G→T点突变是DN并高血压的危险因素。④结论　eNOS基因第 7外显子 894G→T点突变与糖尿病肾病并高血压有关。     

宁夏回族人群CYP3A4*6等位基因多态性的研究

目的 了解宁夏回族人CYP3A4第9外显子的分布特点,为宁夏回族患者使用CYP3M底物药物提供参考依据.方法 收集到180例回族人群血样,应用聚合酶链反应(PCR)特异性扩增人CYP3A4第9外显子基因序列,对其进行测序;同时扩增产物用限制性内切酶HinfⅠ酶切,琼脂糖凝胶电泳后,观察酶切位点的限制性片段长度多态性(RFLP)图谱.结果 运用PCR-RHLP法分析了150例正常回族人、30例高脂血症回族志愿者基因的突变情况,发现有2例第17776位点有A插入引起移码突变,使2例杂合子CYP3A4基因第9外显子提前出现终止密码子.其中野生型纯合子频率为98.9%,杂合子频率为1.1%,突变型纯合子频率为0,突变等位基因频率为0.005.结论 本研究得到了CYP3A4第9外显子基因多态性在宁夏回族人群中的分布情况,为研究CYP3A4第9外显子基因多态性与临床药物效应的相互关系奠定了基础.     

Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase and glutathione S-transferase P1 and chronic obstructive pulmonary disease

Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% -20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione Stransferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113→His), exon 4 (His139→Arg) and GSTP1 polymorphism in exon 5 (Ile105→Val) in 100 COPD patients and 100 age- and sex-matched healthy controls.Results The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32% ). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7. 09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers ( current smokers and exsmokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls.Conclusions mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China.The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.     

Genetic polymorphism in matrix metalloproteinase-9 and the susceptibility to chronic obstructive pulmonary disease in Han population of south China

Theincidenceofchronicobstructivepulmonarydisease(COPD)isincreasingnowandithasbecomeamajorpublichealthproblem ,especiallyforthosesmokers AlthoughthemechanismofCOPDisuncertain ,itisknownthatsmokingisthemajorcausalfactorofCOPD .However,only 1 0 %-2 0 %ofchronicheavycigarettesmokershaveairwayobstructionandrespiratorysymptoms,1　whichshowsthatCOPDisacomplexdiseaseinfluencedbygeneticfactors ,environment,andgenotype environmentinteractions 2 　GeneticfactorsofCOPDindicatethatdifferentgenotyp…     

内皮素受体B的基因多态性与COPD的相关性研究

目的探讨内皮素受体B（endothelin B receotor,EDNRB）基因的第4外显子-30 G／A处单核苷酸多态性与慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）易感性之间关系。方法采用PCR—RFLP技术,检测并分析EDNRB基因-30G／A（L277L）单核苷酸多态性位点在COPD组和健康对照组中的基因型频率、等位基因频率,同时分析该突变位点是否与COPD患者肺功能的下降程度相关。结果研究发现EDNRB基因-30G／A处基因型频率在COPD组和对照组之间的分布存在统计学差异（P〈0．05）,但等位基因频率的分布在两组之间无统计学差异存在（P〉0．05）。此外,COPD患者组中AA基因型组的最大呼气中段流速值（maximal mid—expiratory flow,MMEF）（0．51±0．44）明显小于GG基因型组（1．49±1．70）,且三组之间的差异存在统计学意义（P〈0．05）。结论EDNRB-30G〉A位点处的基因多态性可能与COPD的易感性相关,同时AA基因型与较低的MMEF值相关。     

中国南方汉族人MMP-9基因多态性与COPD易感性的关系

目的探讨中国南方汉族人基质金属蛋白酶-9(MMP-9)基因多态性与慢性阻塞性肺疾病(COPD)易感性的关系.方法应用限制性片段长度多态性(RFLP)技术,检测MMP-9启动子基因型在100例COPD患者和98例健康吸烟者中的频率.结果 COPD中同源野生型(C/C)、杂合型(C/T)频率分别是86%、14%,健康人的频率分别是98%、2%,两组基因频率分布差异具有显著性(P＜0.01).等位基因C频率分别是93%比99%,等位基因T频率分别是7%比1%,两组等位基因的分布差异也具有显著性(P＜0.05).结论 MMP-9启动子-1562位的多态性可能与中国南方汉族人群COPD易感性相关.     

CYP2A6基因多态性与慢性阻塞性肺疾病的相关性研究

目的:探讨细胞色素P4502A6(CYP2A6)基因多态性与慢性阻塞性肺疾病(Chronic Obstructive PulmonaryDisease,COPD)遗传易感性的关系。方法:采用病例-对照研究方法和聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术,分析CYP2A6基因多态性与COPD的关系。结果:COPD组CYP2A6 wt基因型频率高于对照组,两组比较差异有统计学意义,且携带CYP2A6 wt的吸烟者较不吸烟者患COPD的风险增加6.56倍。结论:CYP2A6基因多态性可能与COPD的发病有关;CYP2A6 wt可能是COPD的危险因子,且CYP2A6 wt基因型与吸烟在COPD发病中可能存在交互作用。     

Surfactant protein B 1580 polymorphism is associated with susceptibility to chronic obstructive pulmonary disease in chinese han population

Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population和was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively.The results showed that there was significant difference in genotypes distribution frequency of SPB1580C/T polymorphism locus between COPD smokers and control smokers. C→T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9 % vs 41.7 %, X^2 =4.93, P＜0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1 ％) of SP-B1580-18A/C locus is lower than T allele (70.9 ％) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85 % and 15 % respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.     

白介素-10基因多态性与肺结核病易感性的研究

目的 研究白介素-10(IL-10)基因(-1082 G/A)多态性与肺结核病易感性的关系.方法 利用序列特异性引物多聚酶链反应(RCR-SSP)技术对40例肺结核患者及40例对照人群IL-10(-1082 G/A)多态性进行检测,并对其易感性进行分析.结果 对照组IL-10(-1082 G/A)AA基因型频率(0.825)显著高于患者组(0.55)(P＜0.01).GA基因型患者组显著高于对照组(P＜0.05).患者纽G等位基因频率(0.25)显著高于对照组(0.1)(P＜0.01),RR为1.57,95%CI(1.10～2.24),P＜0.05.结论 IL-10(-1082 G/A)多态性可能与肺结核病的易感性相关,因此其多态性检测可作为遗传标记进行检测,用于早期发现对肺结核病易感的高风险人群,对于结核病防治工作具有重要意义.     

Heat Shock Protein 70 Gene Polymorphisms in Han Nationality of China with Chronic Obstructive Pulmonary Diseases

Summary In order to investigate whether polymorphism in gene for heat shock protein 70 (HSP70) has any bearing on individual susceptibility to the development of chronic obstructive pulmonary disease (COPD), the geotypes of 88 patients with COPD and 87 healthy smoking control subjects were tested by polymerase chain reaction followed by restriction fragment polymorphism analysis for HSP70 gene. In COPD group, HSP70-1 genotype A/A, A/B and B/B was 59. 1%, 35.2% and 5.7%, HSP70-2 genotype A/A, A/B and B/B was 26.1%, 54.6% and 19.3%, and HSP70-hom genotype A/A, A/B and B/B was 70.4%, 27.3% and 2.3% respectively. In the control group, it was 60.9%, 27.5% and 3.5%, 20.7%, 56.3% and 23.0%, and 54.0%, 42.5% and 3.5%, respectively. The frequency of polymorphic genetypes showed no difference between the COPD group and the control group (P>0.05). It was suggested that geneic polymorphism in HSP70 is not associated with development of COPD in Han nationality of China. XIE Jungang, male, born in 1970, M. D., Ph. D. This project was supported by grants from the National Key Technologies R & D Programme of the Tenth Five year Plan [2001 BA 703B03(B)] and the clinical intensive discipline of Ministry of Public Health ([2001]321).     

Heme oxygenase-1 polymorphism associated with severity of chronic obstructive pulmonary disease

Background Recent studies have suggested that susceptibility to chronic obstructive pulmonary disease （COPD） might be related to the length polymorphism of （GT）n repeat in the 5＇-flanking region of heme oxygenase-1 （HOX-1） gene. However, there has been no research about the relationship between the polymorphism of HOX-1 gene and severity of COPD. Methods The polymorphism of HOX-1 gene in 452 patients with COPD from Han population in Southwest China was analysed by fragment analysis. The frequencies of the HOX-1 genotype were compared with the stage of COPD of each patient. Results The HOX-1 genotypes were classified into two groups： group I were individuals with class L allele （the number of GT 〉32 repeats）, and group II were those without class L allele （the number of GT 〈32 repeats）. The genotypic frequency of the HOX-1 group I was significantly higher than group II in the very severe COPD patients （36.8% vs 22.4%, P〈0.01, OR=2.0, 95% CI 1.3-3.1）, while the genotypic frequency of the HOX-1 group II was lower in the mild COPD （16.0% vs 26.0%, P=-0.02, OR=0.5, 95% CI 0.3-0.9）. However, in moderate and severe stages COPD, there were similar genotypic frequencies between HOX-1 group Ⅰ and group Ⅱ. Conclusions Genetic polymorphism in HOX-1 is associated with the severity of COPD in Southwest China. COPD patients with class L allele may be susceptible to develop very severe COPD. Conversely, the COPD patients without class L allele may be more easily stabilized on mild COPD.