新疆地区维汉民族CD14启动子-159位点基因多态性与冠心病的相关性研究

白细胞分化抗原14(CD14)是近年备受关注的一种多功能炎性细胞因子,在动脉粥样硬化过程中起着重要作用.本研究采用PCR-RFLP核苷酸分型技术,研究CD14启动子-159位点多态性与冠心病的关系.     

CD14启动子-260位点基因多态性对糖尿病肾病的影响

目的探讨CD14启动子-260位点基因多态性对糖尿病肾病（DN）的影响。方法应用PCR直接测序法对437例2型糖尿病（T2DM）患者（T2DM组）及145例正常者（对照组）的CD14启动子C-260T基因多态性进行分析。结果两组CD14启动子-260位点基因型分布及等位基因频率均无统计学差异（P〉0．05）;非DN与DN患者比较,其CD14启动子-260位点CC基因与CT＋TT基因有统计学差异（P〈0．05）。结论CD14启动子-260C／T基因多态性与糖尿病发病无相关性,但其CC基因是T2DM患者进展为DN的遗传学风险因素。     

CD14启动子-159位点基因多态性与糖尿病肾病的相关性研究

者在10年和20年时,发生DN的百分率分别为13.3%和23.4%;纯合子CC基因型2型糖尿病患者发生DN的风险高于CT+TT基因型患者.结论 CD14启动子C-159T基因多态性与糖尿病的发病无关,但其中的CC纯合子基因是2型糖尿病患者进展为DN的遗传学风险因素.     

急性脑梗死患者IL-18基因启动子607C／A、137G／C位点多态性观察

目的观察急性脑梗死患者白细胞介素18（IL-18）基因启动子607C／A和137G／C位点单核苷酸多态性（SNP）。方法采用型特异性引物聚合酶链反应（PCR-SSP）技术检测98例脑梗死患者（观察组）和100例健康对照者（对照组）血清IL-18基因启动子607C／A和137G／C位点多态性。结果两组607C／A位点基因型CC、CA和AA的频率及等位基因频率相比P均〉0．05。观察组组137G／C位点GG型频率显著高于对照组,GC型的频率显著低于对照组（P〈0．05）,两组等位基因频率的分布也有显著性差异（P〈0．05）。结论急性脑梗死患者IL-18基因启动子607C／A位点SNP与脑梗死无关,137G／C位点携带等位基因C可能有预防急性脑梗死的作用。     

糖皮质激素对哮喘患者CD4T淋巴细胞和嗜酸细胞活化的影响

为研究口服糖皮质激素泼尼松对哮喘患者体内ＣＤ４Ｔ淋巴细胞，嗜酸细胞活化的影响，用酶联免疫法对治疗前后哮喘患者血清白细胞介素－５，嗜酸细胞阳离子帽白浓度进行了检测。结果表明，口服泼泥松治疗１周后，血清ＩＬ－５，ＥＣＰ浓度降低，提示糖皮质激素可能通过抑制ＣＤ４Ｔ淋巴细胞活化，减少细胞因子的释放而对哮喘发挥抗炎作用。     

中国北方汉族CD14启动子C(-260)T基因点突变及血浆IL-6含量与冠心病的相关性

目的探讨冠心病(CHD)患者CD14启动子C(-260)T基因点突变情况及血浆IL-6含量变化与CHD的相关性。方法采集115例CHD病人和60例健康人抗凝血,用PCR-RFLP法测定CD14启动子C(-260)T基因点突变情况,ELISA法检测血浆IL-6含量。结果CHD组CD14启动子C(-260)T基因点突变频率与对照组无统计学差异(χ2=2.644,P=0.267);CHD组血浆IL-6水平高于健康对照组(t=3.553,P<0.01);CHD病人不同基因型组血浆IL-6含量无统计学差异(F=0.294,P=0.749)。结论CD14启动子C(-260)T基因多态性可能不是CHD的基因决定性危险因子,但作为炎性因子的IL-6在CHD的发生、发展中起着重要的作用,     

中国北方汉族CD14 启动子C(-260)T基因点突变及血浆IL-6含量与冠心病的相关性

目的探讨冠心病（CHD）患者CDl4启动子C（-260）T基因点突变情况及血浆1L-6含量变化与CHD的相关性。方法采集115例CHD病人和60例健康人抗凝血，用PCR-RFLP法测定CDl4启动子C（-260）T基因点突变情况，ELISA法检测血浆IL-6含量。结果CHD组CDl4启动子C（-260）T基因点突变频率与对照组无统计学差异（X^2=2．644，P=0．267）；CHD组血浆IL-6水平高于健康对照组（t=3．553。P〈0．01）；CHD病人不同基因型组血浆IL-6含量无统计学差异（F=0．294，P=0．749）。结论CDl4启动子C（-260）T基因多态性可能不是CHD的基因决定性危险因子，但作为炎性因子的lL-6在CHD的发生、发展中起着重要的作用，     

白细胞介素13基因-1112C/T多态性与支气管哮喘患者发病及血浆总IgE水平的相关性

目的探讨白细胞介素13(IL13)基因启动子区-1112C/T多态性与支气管哮喘(简称哮喘)的相关性及对血浆总IgE水平的影响。方法将哮喘患者(100例)和健康人(100名)被分为哮喘组和对照组,用聚合酶链反应限制性片段长度多态性(PCRRFLP)方法检测哮喘组与对照组-1112位点多态性,用酶联免疫吸附法(ELISA)测定血浆总IgE水平。结果-1112位点等位基因C、T频率在两组间分布的差异具有显著性(χ2=901,P<001),等位基因T与哮喘关联[OR(T/C)=203,95%CI=127～323,P<001]。两组基因型(TT、CT、CC)频率的分布比较差异有显著性(χ2=719,P<005),其优势比OR(TT/CC)=299,95%CI=106～841(P<005);OR(CT/CC)=204,95%CI=109～381(P<005);OR(TT/CT)=146,95%CI=049～437(P>005);在哮喘组CC、CT及TT基因型患者的血浆总IgE水平分别为(204±89)kU/L、(320±108)kU/L、(376±147)kU/L,而在对照组CC、CT及TT基因型患者的血浆总IgE水平分别为(96±34)kU/L、(122±42)kU/L、(150±36)kU/L。同组内T等位基因携带者血浆总IgE水平高于非携带者;同一基因型中哮喘组总IgE水平高于对照组。结论IL13基因-1112位点多态性是影响哮喘的重要候选基因,T等位基因与哮喘关联,并可能通过增强IL13基因的表达影响血浆总IgE水平。     

Association of promoter polymorphism of the CD14 C （-159） T endotoxin receptor gene with chronic hepatitis B

INTRODUCTION An estimated 350 million persons worldwide are infected with hepatitis B virus (HBV). Hepatitis B carriers are at risk for development of cirrhosis and hepatocellular carcinoma. Persons with chronic hepatitis B infection need life-long monito…     

过敏性哮喘儿童血清IL-1β检测水平及基因多态性分析

目的探讨过敏性哮喘儿童血清IL-1β检测水平及基因多态性。方法本院过敏性哮喘儿童78例为病例组,同时选择我院门诊行健康体检的正常儿童67例作为对照组,Elisa法检测病例组及对照组血清IL-1β水平,同时连接酶检测技术检测IL-1β基因的rs1143643、rs11436272多态性。结果病例组血清IL-1β水平高于对照组,差异有统计学意义(P0.05)。病例组IL-1βrs1143643 CC基因型比例高于对照组,IL-1βrs1143643 TT基因型比例低于对照组,其基因分布比较,差异有统计学意义(P0.05);IL-1βrs1143643 CC基因型,能增加过敏性哮喘易感性,差异有统计学意义(P0.05)。病例组IL-1βrs1143643 C等位基因频率比例高于对照组,IL-1βrs1143643 T等位基因频率比例低于对照组,其等位基因频率分布比较,差异有统计学意义(P0.05);IL-1βrs1143643 C等位基因频率能增加过敏性哮喘易感性,差异有统计学意义(P0.05)。病例组IL-1βrs1143627 AA基因型比例与对照组相近,IL-1βrs1143627 GG基因型比例与对照组相近,其基因分布比较,差异无计学意义(P0.05);IL-1βrs1143627 AA基因型不能增加过敏性哮喘易感性,差异无统计学意义(P0.05)。病例组IL-1βrs1143627 A等位基因频率比例与对照组相近,IL-1βrs1143627 G等位基因频率比例与对照组相近,其等位基因频率分布比较,差异无计学意义(P0.05);IL-1βrs1143627 A等位基因频率不能增加过敏性哮喘易感性,差异无统计学意义(P0.05)。病例组IL-1βrs1143643 TT、CT型FEV_1、FEV_1/FVC、FVC水平高于CC型,差异有统计学意义(P0.05);TT型FEV_1、FEV_1/FVC、FVC水平高于CT型,差异有统计学意义(P0.05)。结论过敏性哮喘儿童血清IL-1β水平升高,IL-1βrs1143643 CC基因型能增加过敏性哮喘的易感性,IL-1βrs1143643 TT基因型可能是过敏性哮喘的保护因素;rs1143627 A/T各基因型突变型与哮喘无关联性。     

CD14的基因型及血清水平与急性心肌梗死的关系

目的 研究CD14基因启动子-159C/T、-260C/T多态性各等位基因及基因型在急性心肌梗死(AMI)患者中的分布频率,初步分析其基因型及血清水平与AMI的相关性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测120例AMI患者及130例正常对照组CD14的基因多态性,同时采用酶联免疫吸附试验(ELISA)检测血清CD14水平.结果 AMI组血清CD14水平显著高于对照组(P<0.01),CD14基因-159C/T多态性在AMI组和正常人群中的分布差异无显著性(P>0.05),而CD14基因-260C/T多态性在两组人群中的分布差异存在显著性(P<0.05),等位基因频率的相对风险分析发现,T等位基因携带者患AMI的风险是C等位基因的1.654倍(OR=1.654,95%CI:1.161～2.356),携带T等位基因的AMI患者血清CD14水平显著高于不携带者(P<0.05).结论 CD14基因启动子-260C/T多态性与AMI的发病具有相关性,其中T等位基因可能是AMI发病的遗传易感基因;携带T等位基因的个体可能通过促进CD14的高度表达进而增加了AMI的发病风险.     

Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers

CD14, a co-receptor for endotoxin, plays a significant role in regulating the inflammatory response to this agent. The C-159T single nucleotide polymorphism (SNP) in the CD14 gene promoter is an important regulator of CD14 expression, with TT homozygotes having increased expression of CD14. This SNP has been linked to pathogenesis of asthma and with cardiovascular diseases in smokers. We hypothesize that CD14 also plays a role in the pathophysiology of COPD in smokers who are exposed to endotoxin contained in cigarette smoke as well as endotoxin derived from Gram-negative microbes colonizing their airways. To assess the effect of the C-159T SNP of the CD14 gene promoter on lung function, we recruited 246 smokers 40 years of age or older with a range of 10–156 pack-year smoking exposures. The TT genotype was associated with lower lung function in smokers with a moderate smoking history. However, the CC genotype was associated with decreased lung function in heavy smokers (>56 pack years). The effect of CC genotype on severity of COPD is analogous with the effect of this genotype in risk for asthma. CD14 may be a factor in the pathophysiology of COPD, as it is in asthma and smoking-related cardiovascular diseases.     

Association between CD14 gene promoter polymorphisms with serum total-IgE and eosinophil levels in atopic and non-atopic asthma patients in a Chinese Han population

Objective: The aim of this study was to investigate the association between CD14 gene promoter SNPs with serum total-IgE and eosinophil levels in atopic asthma and non-atopic asthma in Chinese Han. Methods: A total of 152 patients with asthma were divided into atopic asthma (n?=?100) and non-atopic asthma (n?=?52) groups for this study. Six CD14 gene SNPs were analyzed using PCR and gene sequencing. Serum total-IgE and eosinophil levels were measured. The association between genotype frequencies of the CD14 gene loci with total-IgE and eosinophil levels in atopic asthma and non-atopic asthma was evaluated by the ANOVA test method. Hundred and sixteen healthy subjects constitute the control group. Results: We found that serum total-IgE and eosinophil levels were significantly higher in individuals with atopic asthma when compared to individuals with non-atopic asthma (p?<?0.01). For non-atopic asthma, the total-IgE levels of the heterozygous genotypes were significantly higher than the corresponding levels for the homozygous genotypes in CD14-260C?>?T, CD-651C?>?T, CD-911A?>?C and CD-1247A?>?G (p?<?0.01). In atopic asthma, there was no statistical significance for either serum total-IgE or eosinophil levels among the genotypes of the CD14 gene SNPs. In addition, allele A frequency of CD14-1247A?>?G was significantly different between the atopic asthma and non-atopic asthma groups (p?=?0.025). Conclusions: There was a statistical association between the serum total-IgE level and the CD14 gene promoter SNPs in the non-atopic asthma group. The eosinophil level was not found to be statistically associated with the CD14 gene promoter SNPs in either the atopic asthma or non-atopic asthma groups.     

Gene by environment interaction: the -159C/T polymorphism in the promoter region of the CD14 gene modifies the effect of alcohol consumption on serum IgE levels

BACKGROUND: Serum IgE is increased in heavy drinkers. Endotoxin mediates most of the immunological alterations associated with heavy drinking. The -159C/T polymorphism in the promoter region of the gene encoding CD14 (an endotoxin receptor) is associated with serum IgE levels in different populations. AIM: To investigate the possible interaction between alcohol intake and the -159C/T polymorphism in the promoter region of the CD14 gene for serum IgE levels. METHODS: A total of 415 individuals (51.6% males, median age 50 years, range 18-92 years) were studied. A total of 140 individuals were alcohol abstainers, 112 were moderate drinkers (1-280 g/week), and 163 were heavy drinkers (>280 g/week). Main determinations included the CD14/-159C/T genotype, a panel of skin prick tests, total serum IgE, and specific serum IgE against common aeroallergens (Phadiatop test). RESULTS: Heavy drinking was associated with increased total serum IgE values and with positive specific serum IgE to common aeroallergens, but the association was stronger in carriers of the CD14/-159C allele (either CC homozygotes or CT heterozygotes) than in CD14/-159TT homozygotes. Both additive and multiplicative interactions between heavy drinking and the CD14/-159C allele for total and specific serum IgE values was still present after adjusting for potential confounders. Neither alcohol consumption nor the CD14/-159 genotype was associated with skin prick test positivity. CONCLUSIONS: The CD14/-159C/T polymorphism modifies the effect of alcohol consumption on serum IgE levels.     

Relationship between CD14-159C/T gene polymorphism and acute brucellosis risk

Objective:To investigate the association between the cluster of differentiation 14(CD14)-I59C/T(rs2569190) gene polymorphism and susceptibility to acute brucellosis in an Iranian population.Methods:The study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group.Genotyping of the CD 14 variant was performed using an amplification refractory mutation system-polymerase chain reaction method.Results:The prevalence of CD14-159 TT and CT genotypes were associated with increased risk of brucellosis[odds ratio(OR)=l.993.95%confidence interval(95%CD=1.07-3.71.P=0.03 for CT:OR=3.869.95%CI= 1.91-7.84,P=0.01 for TT genotype.Additionally,the minor allele(T) was significantly more frequently present in brucellosis patients than in controls(61%vs.45%.respectively),and was a risk factor for brucellosis(OR=3.058.95%CI= 1.507-6.315.P=0.01).Condusions:The findings provid suggestive evidence of association of the CDI4-159C/T gene polymorphism with susceptibility to acute brucellosis in the Iranian population.     

Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection

AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection. METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls. Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined. RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading. CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.     

肥胖哮喘病人瘦素基因G-2548A位点多态性及水平变化

目的探讨瘦素基因启动子区G-2548A位点多态性和血清瘦素水平变化与肥胖哮喘之间的关系。方法从本实验室哮喘文库中选择研究对象,分为肥胖哮喘、正常体重哮喘、肥胖对照和健康对照四组。根据病情严重程度将正常体重哮喘组分为轻度和中重度持续2个亚组。采用聚合酶链反应-限制性片段长度多态性分析方法测定瘦素基因启动子区G-2548A位点多态性,ELISA法测定瘦素、IL-6及TNF-α水平。同时测定受试者的肺功能。结果 (1)肥胖哮喘和肥胖对照组瘦素基因G-2548A位点AA基因型频率及A等位基因频率与正常对照组比较有显著性差异(χ2=4.167~6.095,P0.05);(2)正常体重哮喘组中的中重度持续亚组AA基因型频率及A等位基因频率与正常对照组比较有显著性差异(χ2=4.080、3.716,P0.05);(3)哮喘组AA基因型与GA+GG基因型组比较,瘦素、IL-6、TNF-α、CRP水平明显升高(P0.01),FEV1%和FEV1/FVC%明显下降(P0.01)。结论瘦素基因启动子区G-2548A位点A等位基因可能是肥胖和哮喘共同的遗传易感因素,瘦素可能是肥胖-哮喘关联路径中的一个重要细胞因子,通过影响其他炎性因子水平变化而在肥胖哮喘的发病机制中发挥重要作用。     

CD40基因-1C/T多态性与急性冠脉综合症遗传易感性的研究

目的探讨CD40基因-1C/T多态性与急性冠脉综合症(ACS)的关系。方法采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测127例急性心肌梗死(AMI)患者(AMI组)、162例不稳定心绞痛(UA)患者(UA组)和159名健康体检者(对照组)CD40基因-1C/T的基因型;酶联免疫吸附试验(ELISA)检测可溶性CD40(sCD40)水平。结果 CD40基因-1位点三种基因型及等位基因频率在AMI组、UA组和健康对照组中分布差异均有统计学意义(P=0.001),相对风险分析显示CC基因型患者AMI和UA的风险分别是TT基因型的6.919和3.073倍;携带C等位基因患者AMI和UA的风险分别是T等位基因型的2.421和1.692倍;sCD40水平在ACS组与对照组间、ACS组内不同基因型者间的分布差异均有统计学意义(P<0.01)。结论 CD40基因-1C/T多态性与ACS的发病具有相关性,C等位基因可能是ACS的遗传易感基因。