严重烧伤患者CD14基因多态性对高迁移率族蛋白B1表达的影响

目的 了解LPS受体CD14C-159T基因多态性对严重烧伤患者伤后高迁移率族蛋白B1(HMGB1)合成、释放的影响以及与脓毒症的关系.方法 采集35例烧伤总面积大于或等于30%TBSA患者伤后1、3、5、7、14、21、28 d静脉血.另设11名志愿者作为健康对照组.采用PCR-限制性片段长度多态性方法检测CD14-159C/T基因多态性,ELISA法检测血浆HMGB1水平,RT-PCR法检测HMGB1 tuRNA表达.对数据行χ~2检验、方差分析和t检验.结果 35例患者的CD14基因C-159T基因型中,CC纯合子型7例占20.0%、TC杂合子型16例占45.7%、TT等位基因纯合子型12例占34.3%.T等位基因和C等位基因分布的频率为57.2%和42.8%.验证表明,此研究群体达到了Hard-Weinberg平衡.在CD14C-159T基因型中,CC纯合子型患者发生脓毒症的概率较TC杂合子型、TT等位基因纯合子型低.3例CC纯合子型脓毒症患者中,仅1例死亡;9例TC杂合子型脓毒症患者中4例死亡;7例TT等位基因纯合子型脓毒症患者中4例死亡.与健康对照组比较伤后1 d患者血浆HMGB1水平即迅速升高,伤后14、21、28 d TC杂合子型、TT等位基因纯合子型患者血浆HMGB1水平均显著高于CC纯合子型(F值为3.5671、4.2035、3.8529,P<0.05或P<0.01).伤后14 d脓毒症组患者外周血白细胞HMGB1 mRNA表达量为1.5±0.5,显著高于非脓毒症组患者(1.2±0.4,t=-2.205,P<0.05).伤后7、21 d脓毒症组患者血浆HMGB1水平分别为(44±29)、(25±15)ng/mL,均高于非脓毒症组患者的(26±12)、(10±6)ng/mL(t值分别为-2.355、-3.872,P<0.05或P<0.01).结论 CD14C-159T基因多态性可显著影响严重烧伤后HMGB1的合成与释放,并与烧伤患者脓毒症易感性有关.     

CD14基因多态性对严重烧伤后CD14表达的影响及其临床意义

目的探讨内毒素受体CD14C-159T基因多态性对烧伤后CD14合成与释放的影响及其与脓毒症易感性、患者预后的关系。方法26例烧伤面积大于30％的患者,采用聚合酶链反应及限制性内切酶HaeuI对PCR产物的消化作用检测CD14基因多态性。同时,对患者白细胞CD14、肿瘤坏死因子-α（TNF-α）mRNA表达,血清sCD14浓度与CD14-159位点基因型以及烧伤患者预后的关系进行了分析。结果Tr、TC、CC三种基因型患者白细胞CD14mRNA、TNF—amRNA表达,血清sCD14浓度存在明显差异。其中Tr、TC基因型CDl4mRNA表达均明显高于CC纯合子（P＜0．05或P＜0．01）,伤后第7天CC基因型血浆sCDl4水平显著低于TC基因型（P＜0．05）;同时,TT纯合子的TNF-αmRNA表达强度明显高于CC纯合子（P＜0．05）。此外,伤后第7、21天死亡组CDl4mRNA表达量显著高于存活组（P＜0．05）。结论CD14C-159T基因多态性可显著影响严重烧伤后CDl4的合成与释放,并与烧伤患者脓毒症易感性有关,T等位基因可能是患者预后不良的高危基因标志物。     

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。     

CD14基因多态性与严重烧伤患者T淋巴细胞免疫功能的相关性研究

目的 探讨严重烧伤患者CD14基因多态性与T淋巴细胞免疫功能的关系.方法 采集77例烧伤体表总面积大于30%患者血标本,通过聚合酶链反应.限制性片段长度多态性方法检测CD14-159C/T基因多态性,观察其外周血T淋巴细胞增殖反应和白细胞介素-2(IL-2)的产生能力,并通过流式细胞仪检测T淋巴细胞CD4+/CD8+的比值、CD4+细胞的凋亡率.结果 严重烧伤后患者T淋巴细胞增殖能力明显下降,与CC纯合子患者比较,TT、TC基因型患者伤后第5、21、28天T淋巴细胞对丝裂原刺激增殖反应显著受抑(P<0.05或P<0.01).烧伤后携带TC、TT型患者IL-2产生一直处于较低水平,而CC型在伤后14 d分泌IL-2逐渐上升.与CC型患者比较,携带TT、TC型患者T淋巴细胞比值均降低,尤其在伤后第1、3、14、21、28天差异明显(P<0.05或P<0.01).三型CD3+CD4+T淋巴细胞凋亡率比较,TT型患者伤后第5、7、21天凋亡率显著高于CC型患者(P<0.05),TC型患者伤后7、14 d其凋亡率高于CC型患者(P<0.05),而,TT、TC型之间上述免疫功能指标比较均无显著差异(P>0.05).结论 CD14-159C/T多态性可影响大面积烧伤患者T淋巴细胞免疫功能状态,进而参与了严重感染并发症的发生与发展过程.     

中国西北部地区汉族患者麻醉药物相关基因多态性的分布

目的对中国西北部地区汉族手术患者OPRM1、CYP3A4*1G、SLCO1B1和ABCB1的基因型种类进行回顾,明确与镇痛和肌松相关的基因突变率。方法西京医院2016年9月至2017年4月籍贯为西北地区省市(陕西、甘肃、宁夏、青海、新疆)的汉族手术患者3 213例,男1 492例,女1 721例,对其OPRM1、CYP3A4*1G、SLCO1B1和ABCB1基因多态性检测结果进行回顾。结果 OPRM1(118AG)突变杂合子AG型的占比为42.11%,突变纯合子GG型的占比为12.14%。CYP3A4*1G的CC、TT、TC、CT的占比分别为29.69%、4.17%、65.67%、0.47%。SLCO1B1杂合子AG型的占比为37.44%,GG型的占比为55.21%。ABCB1的CC、TT、TC、CT的占比分别为13.07%、44.60%、0.28%、42.05%。男性和女性各基因型分布差异无统计学意义。结论西北汉族手术患者中与芬太尼等阿片类药物和罗库溴铵用量相关的4个基因位点突变率均较高,提示基因多态性序列测定指导麻醉用药具有重要临床价值。     

乳腺癌亚甲基四氢叶酸还原酶基因多态性的临床意义

目的：探讨乳腺癌亚甲基四氢叶酸还原酶（MTHFR）基因多态性的临床意义。方法：收集54例乳腺癌女性患者血液样本（研究组）和93例正常女性血液样本（对照组）,均进行DNA提取、PCR扩增、DNA限制性片段长度多态性分析。分析MTHFR C677T、A1298C基因型在乳腺癌女性和正常女性中的分布差异。结果：PCR-RFLP法检测显示,MTHFR基因野生型纯合子CC(198 bp)只有1条带,MTHFR杂合子CT(198 bp、175 bp)产生2条带,MTHFR变异型纯合子TT(175 bp)只有1条带。研究组MTHFR 677CC、677CT和677TT基因型频率分别为37.04%、51.58%和11.11%,677C、677T等位基因频率分别为62.96%、21.51%;对照组MTHFR 677CC、CT和TT基因型频率分别为34.41%、48.39%和17.20%,677C、677T等位基因频率分别为37.04%、41.40%。两组MTHFR C677T基因型频率和等位基因频率比较差异均无统计学意义（P均>0.05）。研究组MTHFR 1298AA、AC、CC基因型频率分别为...     

P-选择素基因多态性与急性胰腺炎相关性分析

目的 ：探讨P-选择素（P-s electin）基因启动子区C-2123G多态性与急性胰腺炎（acute pan-creatitis,AP）发展及预后的相关性。方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RELP）的分析方法,检测102例健康志愿者和119例AP患者P-selectin基因启动子区C-2123G的基因多态性,计算其基因型频率及等位基因频率。结果：健康对照组与AP组C-2123G等位基因频率（C32.35%,G 67.65%）及基因型分布（C纯合子占19.33%,CG占26.05%,G纯合子占54.62%）一致。轻症急性胰腺炎（MAP）组和重症急性胰腺炎（SAP）组等位基因频率及基因型分布差别无统计学意义。发生重症脓毒症患者G等位基因频率（83.33%）高于非脓毒症组（56.76%,P〈0.05）,GG纯合子患者发生重症脓毒症比例高于非脓毒症组（P〈0.05）。结论：P-selectin C-2123G基因多态性在AP发生重症脓毒症中具有重要的作用,是AP病情进展的危险因素。     

严重烧伤后细胞免疫改变及其与高迁移率族蛋白B1的相关性

目的 探讨严重烧伤患者T细胞免疫功能的变化规律及其与高迁移率组蛋白B1(HMGB1)的相关性.方法 采集35例烧伤体表总面积>30%的患者静脉血样,根据是否并发多器官功能障碍综合征(MODS)分组(MODS组13例、非MODS组22例),采集患者伤后第1、3、5、7、14、21、28大的外周静脉血,采用酶联免疫吸附试验检测血浆HMGB1水平;观察外周血T淋巴细胞增殖反应和白细胞介素2(IL-2)的产生能力,并通过流式细胞仪检测CD4+/CD8+T细胞的比值.结果 严重烧伤患者伤后第1天血浆HMGB1水平即明显升高,其中伤后第1、7、21、28天MODS组HMGB1显著高于非MODS组(P<0.05).两组间比较,外周血T淋巴细胞增殖反应和IL-2的产生能力、CIM4+/CD8+T淋巴细胞比值在伤后第1、14、21、28天MODS组显著低于非MODS组(P均<0.05).大面积烧伤患者伤后血浆HMGB1含量与细胞免疫功能指标包括T淋巴细胞增殖活性、IL-2含量、CD4+/CD8+T细胞比值呈显著负相关(P<0.05).结论 大面积烧伤后T淋巴细胞免疫功能紊乱与患者并发MODS密切相关,严重烧伤患者血浆HMGBI水平的持续升高对机体细胞免疫功能异常具有显著影响.     

荆门地区CD14-159C/T多态性和幽门螺杆菌在胃癌中交联作用研究

目的探讨荆门地区人群CD14-159C/T多态性与胃癌关联性及其与幽门螺杆菌交互作用。 方法采用多聚酶链反应-限制性片段长度多态性（PCR-RFLP）方法,分析127例胃癌患者和127名健康者的CD14-159C/T基因型。非条件Logistic分析各基因型与发病中易感性关系以及与幽门螺杆菌的交互作用。 结果携带C（CC/CT）基因个体患病风险较非C基因携带者（TT）风险明显增加（OR=1.35,95% CI=1.22~2.56,P=0.000;校正OR=1.61,95% CI=1.21~3.01,P=0.000）。条件Logistic分析表明,携带CC/CT基因型幽门螺杆菌个体胃癌罹患风险是携带TT基因非幽门螺杆菌个体的3.39倍（OR=3.39,95% CI=2.66~5.36,P=0.000）（RERI=1.94,95% CI=1.41~2.77;API=0.59,95% CI=0.33~0.84;S=1.46,95% CI=1.37~2.66）。 结论CD14-159C/T多态性增加荆门地区个体胃癌的罹患风险,且与幽门螺杆菌在胃癌发病中存在协同效应。     

亚洲人群CYP17(-34T/C)基因多态性与子宫内膜异位症易感性的Meta分析

目的应用Meta分析探讨亚洲人群中细胞色素氧化酶17基因(CYP17)(-34T/C)基因多态性和子宫内膜异位症(EMs)易感性的关系。方法检索Pubmed、中国知网、万方、中国生物医学文献数据库(CBM)等中、英文数据库中发表的关于亚洲人群CYP17(-34T/C)基因多态性和EMs易感性的文献。对文献进行质量评价、筛选和提取相关病例对照研究资料,利用R软件进行Meta分析,计算合并的比数比(OR)及其95%可信区间(CI)。结果共纳入文献6篇,累计病例组662例,对照组937例。分析结果显示:等位基因对比模型(T vs.C):OR=1.283,95%CI:0.948-1.737;杂合子模型(TC vs.CC):OR=1.181,95%CI:0.919-1.518;纯合子模型(TT vs.CC):OR=1.612,95%CI:0.899-2.889;显性模型(TT+TC vs.CC):OR=1.320,95%CI:0.932-1.871;隐性模型(TT vs.TC+CC):OR=0.716,95%CI:0.456-1.123。结论本次Meta分析结果显示,在亚洲人群中CYP17(-34T/C)基因多态性与EMs易感性并无显著相关性,但需要开展更多设计细致、实施良好的大样本量病例-对照研究以得到更科学可信的结论。     

Association between decreased kidney function and endotoxin receptor CD14 C-159T polymorphism among Japanese health check-up examinees

BACKGROUND: A recently identified promoter polymorphism of the endotoxin receptor (CD14 C-159T) was shown to be associated with atherosclerotic diseases such as myocardial infarction. This study was conducted to determine whether this polymorphism is associated with decreased kidney function. METHODS: A total of 281 male and 522 female health check-up examinees, aged 39-88 years, were genotyped for CD14 C-159T. The glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease (MDRD) Study equation. Estimated GFR (eGFR) and the proportion of subjects with mildly decreased eGFR (eGFR under 90 mL/min/1.73 m(2)) were compared among the genotypes. RESULTS: Subjects carrying the T allele showed decreased age- and sex-adjusted eGFR compared with those with CC genotype (101+/-22 vs. 105+/-23 mL/min/1.73 m(2); mean+/-SD, p = 0.012). The proportion of subjects with mildly decreased eGFR was higher in T allele carriers (34.2% for TT+CT and 26.3% for CC genotype, p = 0.041), but not statistically significant when adjusted for age and sex (odds ratio [OR] 1.41, 95% CI 0.97-2.05, p = 0.076). In subjects under 65 years, T allele carriers had a significantly increased risk for mildly decreased eGFR (27.1% for TT+CT and 18.0% for CC; age- and sex-adjusted OR 1.82, 95% CI 1.06-3.12, p = 0.030). CONCLUSION: CD14-159T allele was associated with decreased eGFR compared with CC genotype, and with a higher prevalence of mildly decreased eGFR in younger subjects under 65.     

Influence of CD14 polymorphism on CD14 expression in patients with extensive burns

We sought to investigate the association of CD14 genotype with the risk of mortality after burn, and we also attempted to evaluate whether CD14-159 C/T polymorphism affects the kinetics and extent of CD14 expression as well as its release, and TNF-alpha expression in burned patients. The study involved 64 patients in Chinese Han population incurring burns covering more than 30% of the total body surface area. CD14 polymorphism was determined by polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) analysis. Meanwhile, leukocyte CD14 mRNA expression and soluble CD14 (sCD14) levels were measured during a 28-day observation period. TNF-alpha mRNA and protein levels were also determined in patients with different genotypes of CD14. On day 21 after burn, CD14 mRNA expression and sCD14 levels were significantly higher in TT homozygotes than in CC genotypes (1.33+/-0.36 microg/ml vs. 0.75+/-0.28 microg/ml and 16.1+/-4.6 microg/ml vs. 9.7+/-3.4 microg/ml, P<0.05), and these values were also higher in non-survivors than in survivors (1.32+/-0.40 microg/ml vs. 0.87+/-0.32 microg/ml and 14.8+/-4.5 microg/ml vs. 11.1+/-4.8 microg/ml, P<0.05). In addition, TNF-alpha mRNA and protein levels were significantly lower in both CC homozygotes and survivors than in TT genotypes or non-survivors during the 28-day observation period (P<0.05). However, TT genotype did not impart an increased risk for burn mortality in this small study. In conclusion, CD14-159 C/T polymorphism might be associated with the kinetics and extent of CD14 expression as well as its release, and it was also related to TNF-alpha expression. However, this study did not confirm CD14-159 C/T polymorphism was associated with the outcome of extensive burns.     

Association between Decreased Kidney Function and Endotoxin Receptor CD14 C-159T Polymorphism among Japanese Health Check-up Examinees

Background. A recently identified promoter polymorphism of the endotoxin receptor (CD14 C-159T) was shown to be associated with atherosclerotic diseases such as myocardial infarction. This study was conducted to determine whether this polymorphism is associated with decreased kidney function. Methods. A total of 281 male and 522 female health check-up examinees, aged 39–88 years, were genotyped for CD14 C-159T. The glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease (MDRD) Study equation. Estimated GFR (eGFR) and the proportion of subjects with mildly decreased eGFR (eGFR under 90 mL/min/1.73 m²) were compared among the genotypes. Results. Subjects carrying the T allele showed decreased age- and sex-adjusted eGFR compared with those with CC genotype (101±22 vs. 105±23 mL/min/1.73 m²; mean±SD, p?=?0.012). The proportion of subjects with mildly decreased eGFR was higher in T allele carriers (34.2% for TT+CT and 26.3% for CC genotype, p?=?0.041), but not statistically significant when adjusted for age and sex (odds ratio [OR] 1.41, 95% CI 0.97–2.05, p?=?0.076). In subjects under 65 years, T allele carriers had a significantly increased risk for mildly decreased eGFR (27.1% for TT+CT and 18.0% for CC; age- and sex-adjusted OR 1.82, 95% CI 1.06–3.12, p?=?0.030). Conclusion. CD14-159T allele was associated with decreased eGFR compared with CC genotype, and with a higher prevalence of mildly decreased eGFR in younger subjects under 65.     

Association of transforming growth factor beta1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis.

Transforming growth factor beta (TGF-beta) is an important regulator of bone metabolism, its effects being intertwined with those of estrogen and vitamin D. A T-->C polymorphism in exon 1 of the TGF-beta1 gene, which results in the substitution of proline for leucine, is associated with bone mineral density (BMD). However, it is not known whether this polymorphism affects the response to treatment with active vitamin D or to hormone replacement therapy (HRT) in individuals with osteoporosis. Changes in BMD at the lumbar spine (L2-L4 BMD) were compared among TGF-beta1 genotypes in 363 postmenopausal Japanese women who were divided into three groups: an untreated, control group (n = 130), an active vitamin D treatment group (n = 117), and an HRT group (n = 116). TGF-beta1 genotype was determined with an allele-specific polymerase chain reaction assay. In the control group, the rate of bone loss decreased according to the rank order of genotypes TT (homozygous for the T allele) > TC (heterozygous) > CC (homozygous for the C allele), with a significant difference detected between the CC and TT genotypes. The positive response of L2-L4 BMD to HRT increased according to the rank order of genotypes TT < TC < CC, although the differences among genotypes were not statistically significant. Individuals with the CC genotype responded to active vitamin D treatment with an annual increase in L2-L4 BMD of 1.6%, whereas those with the TT or TC genotypes similarly treated lost bone to a similar extent as did untreated subjects of the corresponding genotype. These results suggest that TGF-beta1 genotype is associated with both the rate of bone loss and the response to active vitamin D treatment.