CD14C(-260)T基因多态性、循环中可溶性CD14水平与动脉粥样硬化

Background: CD14 pathway is at the crossroads between infection and inf lammati on. In human pathology, divergent results have been reported on the relationship between a polymorphism in the promoter of receptor CD14 (C260T), expression of soluble CD14(sCD14) receptor and atherosclerosis. The aim of the study was to in vestigate in a cross-sectional population-based sample the relationships betwe en C260T polymorphism in CD14 gene, sCD14 blood levels and arterial wall. Method s: Among 1015 subjects, randomly recruited by the Toulouse MONICA center between 1995 and 1997, 899 subjects with complete data for all the measurements, were a nalyzed. sCD14 was measured using an immunoenzymatic method. Common carotid inti ma-media thickness (IMT) and the presence of plaques in the carotid and femoral arteries were assessed by ultrasonography. A genotypic examination for the CD14 C260T polymorphism was performed. Results: An increase in sCD14 expression was observed in subjects carrying t allele (P < 0.01). No significant difference in intima-media thickness, number of plaques and pulse wave velocity was noticed a ccording to C260T polymorphism. An interaction (P < 0.05) was observed between C 260T polymorphism and current smoking in sCD14 expression: among smokers, no sig nificant change in sCD14 was observed in individuals carrying t allele. Conclusi on: Although (C260T) polymorphism in CD14 gene in this study is associated with expression of sCD14, no significant association was found between this polymorph ism and early markers of atherosclerosis. This polymorphism affects plasma level s of sCD14 in relation to current smoking status. Further studies are needed to determine whether this interaction influences the deleterious effect of smoking on vascular events.

Meta分析CD14基因-159C/T多态性与变应性鼻炎易感性关系

目的Meta分析CD14基因-159C/T多态性与变应性鼻炎(AR)易感性关系,为AR的发病机制及疾病预防提供理论依据。方法检索PubMed、EMBASE、Cochrane等国外数据库及中国期刊全文数据库、中国科技期刊数据库、中国生物医学文献数据库、万方数字期刊全文数据库等中文数据库中发表的CD14基因-159C/T多态性与变应性鼻炎易感性关系的病例对照研究。根据纳入和排除标准对文献进行筛选,用Jadad quantity对纳入的文献进行偏差评估和敏感性分析,用Revman5.3软件对数据进行处理。结果根据纳入和排除标准,共纳入9篇文献,共2319名受试者,其中病例组1195例,对照组1124例。Meta分析结果显示:优势基因模型下(CC vs CT+TT),组合OR值为0.74,95%CI为[0.61,0.90],P=0.002,差异有统计学意义;超显性基因模型下(CT vs CC+TT),联合OR值为1.12,95%CI为[0.95,1.32],P=0.18,差异无统计学意义;隐性基因模型下(TT vs CC+CT),联合OR值为1.14,95%CI为[0.95,1.38],P=0.15;等位基因(C对T),合并OR值为0.95,95%CI为[0.83,1.10],P=0.50,差异无统计学意义。表明与T等位基因相比,在a位点携带C等位基因不会增加AR的易感性。优势基因模型可能增加基因型CD14基因-159C/T的AR易感性,而隐性基因模型和超显性基因模型可能不会增加基因型CD14基因-159C/T的AR易感性。结论CD14基因-159C/T多态性与AR易感性无显著相关性。基因座中的基因型可能增加AR易感性的基因模型是优势基因模型。

CD14基因-159C/T多态性与变应性鼻炎易感性关系的meta分析

目的探讨CD14基因-159C/T多态性与变应性鼻炎(AR)发病风险的相关性。方法检索中国学术期刊文献数据库和PubMed,Embase等查找有关CD14基因-159C/T多态性与AR易感性关系的病例对照研究,采用Stata l5.0统计学软件进行meta分析。结果最终共纳入9篇文献,均为病例对照研究,其中病例组1195例、对照组1124例。meta分析总体结果:T vs C等位基因和4种基因模型在病例组和对照组间的差异无统计学意义。此外,按对照组来源和单核苷酸多态性(SNP检测法)进行亚组分析:T vs C等位基因和各基因模型在病例组和对照组间的差异无统计学意义。当按种族进行亚组分析时发现,在非洲人群中,等位基因T vs C(OR=2.05,95%CI:1.47~2.86;P<0.05)、显性模型TT+CT vs CC(OR=2.00,95%CI:1.24~3.22;P=0.004)、隐性模型TT vs CC+CT(OR=4.04,95%CI:2.02~8.09;P<0.05)、TT vs CC(OR=5.02,95%CI:2.37~10.63;P<0.05)在病例组和对照组间的差异有统计学意义,而CT vs CC(OR=1.48,95%CI:0.89~2.45;P=0.129)差异无统计学意义。在亚洲人群中,病例组和对照组间的差异均无统计学意义。结论亚洲人群中,CD14基因-159C/T多态性与AR易感性无明显相关性;非洲人群中埃及儿童CD14基因-159位点的T等位基因与特应性哮喘和AR有关,TT基因与烟草烟雾暴露儿童免疫球蛋白E(IgE)水平升高有关。

CD14启动子-260C/T基因多态性与胃癌易感性的Meta分析

目的 CD14启动子-260C/T基因多态性与胃癌易感性的关系已被广为研究,但是其结果并不尽相同.为了更精确评估二者的关系,笔者进行了Meta分析.方法 计算机全面检索PubMed、Medline、EMbase、CBM、CNKI、万方和维普等数据库,并辅以手检.检索时间从建库截至2015年1月1日,收集CD14启动子-260 C/T基因多态性与胃癌易感性病例对照研究.采用RevMan 5.2软件计算合并效用量OR及其95％ CI,采用Stata 12.0合成漏斗图.结果 共纳入10个研究,其中病例组2365例,对照组3497例.Meta分析发现,在4个遗传模型中,CD14启动子-260C/T基因多态性与胃癌风险的相关性差异均无统计学意义（显性模型：OR=1.07,95％ CI：0.83 ～1.39;隐形模型：OR=1.08,95％ CI：0.89 ～ 1.30;TT vs CC模型OR=1.11,95％ CI：0.79～1.56;CTvsCC模型：OR=1.06,95％CI：0.83 ～ 1.35）.进一步以种族及对照来源行分层分析,亦未发现CD14启动子-260 C/T基因多态性与胃癌风险存在相关性（显性模型：HB对照源：OR=1.02,95％CI：0.63 ～ 1.65,PB对照源：OR=1.12,95％CI：0.85 ～ 1.49;亚洲人：OR=1.12,95％CI：0.73 ～ 1.71;白种人：OR=1.02,95％CI：0.80 ～1.30）.结论 CD14启动子-260C/T基因多态性与胃癌易感性无关,基因型TT和CT＋ TT并不增加罹患胃癌的风险.

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

AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.

Toll样受体2基因Arg753Gln和CD14启动子-159C/T多态性与肺炎链球菌病易感性的Meta分析

目的评价Toll样受体2基因Arg753Gln和CD14启动子-159C/T多态性与肺炎链球菌病易感性的相关性。方法检索PubMed、Cohrance、Embase、CNKI、维普、万方等数据平台,检索文献时间限定为从建库到2017年6月1日。搜寻符合纳入和排除条件的随机对照研究,RevMan 5.3软件进行Meta分析。结果纳入TLR2有关论文3篇,样本量总计为951例;纳入CD14相关研究2篇,样本量总计为674例。Meta分析未见TLR2基因Arg753Gln多态性和CD14-159C/T多态性与肺炎链球菌病易感性相关(显性等位基因vs.隐性等位基因:OR=0.76,95%CI=0.40～1.46,P=0.41;显性基因型vs.隐性基因型时,OR=0.70,95%CI=0.34～1.44,P=0.33)。结论未见TLR2基因Arg753Gln和CD14-159C/T多态性与肺炎链球菌病易感性相关。

CD14-159C/T基因多态性对全血培养CD14表达的影响

目的探讨CD14基因启动子-159C/T基因多态性对全血培养CD14mRNA表达及可溶性CD14(sCD14)浓度的影响。方法采集118例健康献血员血标本,用全血细胞培养模型检测内毒素刺激前后CD14mRNA表达及sCD14浓度的变化。采用聚合酶链反应(PCR)及限制性内切酶HaeⅢ对PCR产物的消化作用检测CD14基因多态性。同时,对内毒素刺激后肿瘤坏死因子α(TNF-α)诱生水平进行了分析。结果118例健康献血员中,等位基因T和C的频率分别为60.2%和39.8%;40例是T等位基因纯合子(TT),62例为杂合子(TC),还有16例基因型为CC。基因型TT与TC白细胞中CD14mRNA的表达及上清液sCD14浓度均明显高于CC纯合子(P<0.05或0.01)。并且TT纯合子TNF-α诱生水平为(352±215)pg/ml,显著高于基因型TC及CC[(261±163)pg/ml及(198±122)pg/ml,P<0.05]。结论内毒素受体CD14-159C/T基因多态性对全血培养CD14的表达及释放产生显著影响,并与内毒素诱导TNF-α的反应性相关。

脂多糖受体CD14基因启动子-159位点C/T基因多态性对高糖低脂膳食诱导的健康青年血脂比值变化的影响

目的探讨CD14启动子-159位点C/T多态性对健康青年血脂比值的影响及在高糖低脂(highcarbohydrate/low fat,HC/LF)膳食诱导的血脂比值变化中的作用。方法纳入56名(22.89±1.80岁)健康青年志愿者,先后给予7d平衡膳食和6dHC/LF膳食,于第1d、第8d及第14d清晨抽取12h空腹静脉血,测定血脂水平,计算甘油三酯/高密度脂蛋白胆固醇(triglyceride/high density lipoprotein-cholesterol,TG/HDL-c)、log(TG/HDL-c)、总胆固醇/高密度脂蛋白胆固醇(total cholesterol/high density lipoprotein-cholesterol,TC/HDL-c)和低密度脂蛋白胆固醇/高密度脂蛋白胆固醇(low density lipoprotein-cholesterol/high density lipoprotein-cholesterol,LDL-c/HDL-c)。提取基因组DNA,聚合酶链反应-限制性酶切法分析CD14启动子-159位点多态性。结果女性TT纯合子受试者TG/HDL-c(P<0.05),log(TG/HDL-c)(P<0.05)和LDL-c/HDL-c(P<0.05)基础值高于C等位基因携带者,男性C等位基因携带者TG/HDL-c(P<0.05)、log(TG/HDL-c)(P<0.001)和TC/HDL-c(P<0.01)高于女性。HC/LF膳食前,女性TT纯合子受试者TG/HDL-c(P<0.01)、log(TG/HDL-c)(P<0.001)和TC/HDL-c(P<0.05)均高于C等位基因携带者,男性C等位基因携带者4种血脂比值均高于女性(P<0.05)。HC/LF膳食后,女性TT纯合子受试者TG/HDL-c(P<0.05)、log(TG/HDL-c)(P<0.05)和LDL-c/HDL-c(P<0.05)均高于C等位基因携带者,男性C等位基因携带者TG/HDL-c(P<0.05)、log(TG/HDL-c)(P<0.01)高于女性。与HC/LF膳食前相比,HC/LF膳食后男性C等位基因携带者TC/HDL-c(P<0.001)、LDL-c/HDL-c(P<0.01)降低,TT纯合子受试者TC/HDL-c(P<0.001)降低。HC/LF膳食后女性C等位基因携带者TG/HDL-c(P<0.05)、log(TG/HDL-c)(P<0.05)升高,TC/HDL-c(P<0.001)、LDL-c/HDL-c(P<0.01)降低,TT纯合子受试者只有TC/HDL-c(P<0.01)降低。结论相较于T等位基因携带者,C等位基因携带者中,膳食改变对血脂表型的作用是微效,可能被CD14-159位点C等位基因掩盖。HC/LF膳食与CD14-159位点C等位基因的相互作用能够降低青年男女LDL-c/HDL-c,升高女性TG/HDL-c和log(TG/HDL-c)。