细胞间黏附分子-1基因K469E多态性与冠心病关系的研究

目的：探讨细胞间黏附分子-1（ICAM-1）基因K469E多态性在冠心病及正常人群中的分布，初步分析其基因型及血清水平与冠心病的关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术和DNA序列测定法，检测了225例冠心病患者和230例对照者的ICAM-1基因K469E多态性，并用酶联免疫吸附试验检测了ICAM-1的血清水平。结果：冠心病组血清ICAM-1水平显著高于对照组（P〈0．01），ICAM-1基因型及等位基因的分布频率在冠心病组和对照组间比较差异具有显著性（P〈0．05），K等位基因携带者患冠心病的相对风险度是E等位基因的1．430倍（与对照组相比），而患心肌梗死的相对风险度是1．816倍（与心绞痛组相比）。结论：ICAM-1基因K469E多态性与冠心病的发生、发展及该疾病的严重程度密切相关，其中K等位基因可能是冠心病发病的遗传易感基因。     

细胞间黏附分子-1基因K469E多态性与类风湿性关节炎的关系

目的 探讨细胞间黏附分子-1(intercelluhr adhesion molecul-1,ICAM-1)基因K469E多态性与类风湿性关节炎(rheumatoid arthritis,RA)的关系.方法 对275例类风湿性关节炎患者和254名体检健康者作为对照组进行研究.采用聚合酶链反应-限制性片段长度多态性方法分析ICAM-1基因K469E的多态性.结果 RA组K469E位点KK、KE和EE基因型频率为0.535、0.411和0.054;健康对照组K469E位点KK、KE和EE基因型频率为0.512、0.437和0.051.RA组K469E基因型频率与健康对照组相比差异无统计学意义(x2=0.371,P=0.831).RA组K等位基因频率(0.74)与健康对照组(0.73)相比差异无统计学意义(x2=0.127,P=0.721,OR=1.051,95%CI为0.800～1.381),在RA组中KK+KE基因型频率与对照组相比,差异无统计学意义(P=0.863,OR=0.935,95%CI为0.436～2.005).结论 ICAM-1基因K469E多态性分布与RA的易感性无明显相关性.

Abstract：

Objective To investigate the association of the intercellular adhesion molecule-1 gene (ICAM-1)K469E polymorphism and rheumatoid arthritis (RA). Methods Two hundred and seventy five patients with RA and 254 healthy individuals were collected and enrolled in the study. The K469E polymorphism of ICAM-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The genotype frequencies of KK, KE and EE of K469E polymorphism were 0. 535,0.411 and 0. 054 respectively in the RA patients, and 0. 512,0. 437 and 0. 051 respectively in the healthy individuals, and there was no significant difference between the two groups (x2 =0. 371,P=0. 831). The frequencies of the K469 allele were 0. 74 and 0. 73 in the RA patients and the controls respectively (x2 = 0. 127, P = 0. 721, OR = 1.051,95 % CI: 0. 800-1. 381 ). No significant difference was observed in KK+KE genotype frequencies between the two groups (P=0. 863), with an odds ratio of 0. 935 (95% CI: 0. 436-2.005). Conclusion The K469E polymorphism of the ICAM-1 gene was not associated with the susceptibility of rheumatoid arthritis.     

冠状动脉粥样硬化性心脏病细胞问黏附分子1基因K469E多态性的研究

OBJECTIVE: To study the linkage between K469E polymorphism of intercellular adhesion molecule 1(ICAM1) gene with ICAM1 plasma level and coronary heart disease (CHD) in Han population of China. METHODS: One hundred and sixty-four controls without CHD and 160 patients with CHD were enrolled in our study. By nested PCR with allele-specific oligonucleotide primers, all patients and controls were genotyped for the ICAM1 polymorphism. And the ICAM1 plasma level was measured by ELISA. RESULTS: In the patients with CHD, both K allele frequency and the plasma level of ICAM1 were higher than those in control (P<0.05). The individual with K allele had higher plasma level of ICAM1 than that without K allele (344.34+/-128.59 microg/L vs 303.54+/-108.74 microg/L, P=0.008). K allele enhanced the risk of CHD (P<0.01, OR=2.158, 95%CI: 1.250-3.727). There was the K allele cooperation with smoking in influencing the risk of CHD. CONCLUSION: There is the polymorphism of ICAM1 K469E gene in Han population of China, and the K allele may be a genetic factor influencing the risk of CHD.     

细胞间黏附分子1基因K469E多态性与冠状动脉粥样硬化性心脏病的关联研究

目的研究中国汉族人群中细胞间黏附分子1（intercellular adhesion moleculel，ICAM1）基因K469E多态性与冠状动脉粥样硬化性心脏病（简称冠心病）的关联。方法采用聚合酶链反应．限制性片段长度多态性方法检测了173例冠心病患者和141名对照的ICAM1基因K469E基因型和等位基因的分布。结果基因型频率符合Hardy-Weinberg平衡。冠心病组的KK基因型的频率显著高于对照组（64．2％比48．9％，P〈0．01），同样，冠心病组K等位基因的频率显著高于对照组（79．2％比69．9％，P〈0．01）。经Logistic回归分析排除年龄，性别，和冠心病其它危险因素的影响后，KK纯合子患冠心病的危险性是KE和EE基因型的2．35倍（95％CI：1．03-5．36，P〈0．05）。结论ICAM1基因K469E多态性与中国汉族人冠心病的危险性相关，其中K等位基因可能是冠心病的遗传危险因素。     

冠状动脉粥样硬化性心脏病细胞间黏附分子1基因 K469E多态性的研究

目的探讨细胞间黏附分子1(intercellularadhesionmolecule1,ICAM1)基因K469E多态性及其血浆水平与中国汉族冠状动脉粥样硬化性心脏病(简称冠心病)之间的关系。方法利用巢式PCR和免疫酶联吸附测定技术对160例冠心病患者和164名非冠心病对照进行ICAM1基因K469E多态性及其血浆水平的检测和对比分析。结果冠心病组K等位基因频率、ICAM1血浆水平均高于非冠心病对照组(P<0·05);含K等位基因的个体ICAM1血浆水平(344.34±128.59μg/L)高于不含K等位基因的个体(303·54±108·74μg/L),差异有统计学意义(P=0.008);且其患冠心病(心肌梗塞)的危险性升高(P=0.006,OR=2·158,95%CI:1.250~3.727);K等位基因与吸烟在影响冠心病发生危险性方面有协同作用。结论在中国汉族人群中存在ICAM1基因K469E多态性,其中K等位基因有可能是冠心病的遗传危险因素。     

广西壮族人群ICAM-1基因多态性及血清水平与脑梗死关系的研究

探讨细胞间黏附分子1(ICAM-1)基因K469E多态性各等位基因及基因型在广西壮族脑梗死患者中的分布频率,初步分析其基因及血清水平与脑梗死的关系。采用聚合酶连反应-限制性片段长度多态性(PCR-RFLP)和DNA序列测定法检测19例脑梗死及210例对照者ICAM-1基因第6外显子K469E多态性,同时采用酶联免疫吸附试验(ELISA)检测脑梗死和对照者血清ICAM-1水平。脑梗死组ICAM-1血清水平显著高于对照组(P<0.01),ICAM-1基因K469E基因频率和等位基因频率在脑梗死组和对照组比较差异有显著性(P<0.05),等位基因频率的相对风险分析发现,E等位基因携带者患脑梗死的风险是K等位基因的1.454倍(OR=1.454,95%CI1.090～1.940),携带E等位基因的脑梗死患者ICAM-1血清水平显著高于不携带者(503.31±141.32)ng/ml和(489.80±122.43)ng/ml,(P<0.01)。ICAM-1基因K469E多态性与脑梗死的发病具有相关性,E等位基因可能是广西地区壮族人脑梗死发病的遗传易感基因,携带E等位基因的个体可能通过促进ICAM-1的高度表达进而增加脑梗死的发病风险。     

细胞间黏附分子-1基因K469E多态性与广西壮族人群缺血性脑卒中的遗传易感性

目的探讨细胞间黏附分子-1(intercellular adhesion molecule-1, ICAM-1)基因多态性与广西地区壮族人群缺血性脑卒中(ischemic stroke,IS)的关系.方法采用聚合酶链反应-限制性片段长度多态性和DNA序列测定法检测205例IS及210名对照者 ICAM-1基因第6外显子K469E多态性,同时采用酶联免疫吸附试验检测IS和对照者血清ICAM-1水平. 结果 IS组ICAM-1血清水平显著高于对照组(P<0.01), ICAM-1基因K469E基因型频率和等位基因频率在IS组和对照组比较差异有统计学意义(P<0.05),等位基因频率的相对风险分析发现,E等位基因携带者患IS的风险是K等位基因的1.424倍(OR=1.424,95%CI1.071～1.894),携带E等位基因的IS患者ICAM-1血清水平显著高于不携带者[(501.24±139.56)ng/ml vs(475.17±118.35)ng/ml, P<0.01]. 结论 ICAM-1基因K469E多态性与IS的发病具有相关性,E等位基因可能是广西地区壮族人群IS发病的遗传易感基因,携带E等位基因的个体可能通过促进 ICAM-1的高度表达进而增加IS的发病风险.     

细胞间黏附分子-1基因多态性与缺血性心脑血管疾病

细胞间黏附分子-1在炎症早期介导白细胞与受损内皮细胞的黏附，由于其基因多态性影响了缺血性心脑血管疾病的发生和预后，成为研究热点。本文就该研究领域的新进展做一综述。     

细胞间黏附分子-1基因多态性与疾病易感性

细胞间黏附分子-1(ICAM-1)属于免疫球蛋白超家族成员之一，是一种细胞表面单链糖蛋白，它表达于多种细胞表面，通过识别其受体LFA-1、MAC-1、P150、P95介导细胞-细胞间的黏附，参与多种炎症反应及免疫过程。不同种族和地区研究证实ICAM-1基因多态性与人类多种疾病相关。     

细胞间粘附分子-1基因K469E多态性与冠脉支架置入后再狭窄相关性的初步探讨

目的 探索细胞间粘附分子-1基因K469E多态性与冠脉支架置入我院病人术后再狭窄的相关性.方法 通过收集手术相关因素信息、传统危险因素,并结合冠脉支架术后行冠脉造影随访的116例我院患者的术后情况,应用PCR-RFLP方法确定ICAM-1K469E基因型.结果 随访的116例病人中无再狭窄患者48例,其KK纯合子和E等位基因携带基因型的频率分别为60.4%和39.6%;再狭窄患者68例,其二者的频率分别为41.2%和58.8%.二者的分布有显著性差异(P=0.046).危险因素分层发现在高脂血症和肥胖病人的OR值分别为9.2、3.6(P值均小于0.05),KK纯合子的再狭窄危险更高.结论 ICAM-1469KK纯合子冠脉支架置入后再狭窄危险性较高,其中肥胖或高脂血症病人表现更为明显.     

No association of the MCP-1 promoter A-2518G polymorphism with bipolar disorder in the Korean population

It has been suggested that bipolar disorder is associated with altered immune function. Monocyte chemoattractant protien-1 (MCP-1) is a chemokine that influences both neural and immune functions. We thus hypothesized that MCP-1 may be related to the development or pathophysiology of bipolar disorder. In this case–control study, we investigated the association between the A-2518G single nucleotide polymorphism (SNP) of the MCP-1 promoter and bipolar disorder. Patients with bipolar disorder (n = 183; bipolar I = 145, bipolar II = 38) and healthy controls (350) were recruited for the study. No significant allelic or genotypic association was detected between the A-2518G polymorphism and any sample of bipolar disorder patients. When we pooled the healthy controls and the cases of bipolar I disorder from previous Korean studies and this study, we again found no significant association. No significant difference in either allele frequency or genotype distribution was observed between bipolar I and bipolar II disorders. There was no difference in the age at onset of bipolar disorder among the three genotype groups. Our data suggest that the A-2518G polymorphism of MCP-1 is not a major susceptibility factor for bipolar disorder in the Korean population. However, the physiological role of MCP-1 is highly suggestive of its being associated with bipolar disorder, and further analyses of other SNPs of MCP-1 remain to be performed.     

Synergistic effect of interleukin-6 promoter (IL6 -634C/G) and intercellular adhesion molecule-1 (ICAM-1 469K/E) gene polymorphisms on the risk of endometriosis in Japanese women

PROBLEM: Endometriosis is an immune-related, chronic inflammatory disease with a polygenic predisposition. The aim of this study was to investigate whether the interleukin-6 (IL-6) gene promoter region polymorphism (-634C/G) and the intercellular adhesion molecule-1 (ICAM-1) gene 469K/E polymorphism are responsible in part for the genetic susceptibility to endometriosis. METHODS OF STUDY: The IL-6 -634C/G and ICAM-1 469K/E genotypes were determined in 202 patients with endometriosis and 236 control women by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no differences in the IL-6 -634C/G or the ICAM-1 469K/E genotypes and allele frequencies between control women and endometriosis patients collectively, or between control women and each clinical subgroup of endometriosis patients. Interestingly, the frequency of ICAM-1 EE homozygotes who concomitantly carried the IL-6 -634G allele was significantly higher in patients with endometriosis (chi(2) = 6.458, P = 0.0396, d.f. = 2). CONCLUSION: Our results suggest that the IL-6 -634C/G and ICAM-1 469K/E polymorphisms synergistically affect the susceptibility for endometriosis in the Japanese population.     

血管紧张素-(1-7)对血管紧张素Ⅱ诱导的脐静脉内皮细胞MCP-1和ICAM-1表达的影响

目的： 研究血管紧张素-(1-7)［Ang-(1-7)］对血管紧张素Ⅱ（AngⅡ）诱导的脐静脉内皮细胞（HUVEC）单核细胞趋化蛋白-1（MCP-1）和细胞间黏附分子-1（ICAM-1）的影响,阐明Ang-(1-7)对AngⅡ在炎症方面的拮抗作用。方法: 体外培养HUVEC,随机分为：对照组;AngⅡ组;Ang-(1-7)组;AngⅡ+Ang-(1-7)组;AngⅡ+ Ang-(1-7) + Ang-(1-7)受体阻断剂A-779组。以ELISA法和半定量RT-PCR法从蛋白和mRNA水平检测MCP-1和ICAM-1的表达情况。结果: 与对照组比,AngⅡ（100 nmol/L）使MCP-1和ICAM-1的蛋白和mRNA表达明显增加（P<0.05）;Ang-(1-7)（1 000 nmol/L）使MCP-1和ICAM-1的蛋白和mRNA表达降低（P<0.05）;混合刺激组中,与AngⅡ组比较,Ang-(1-7) （10 nmol/L、100 nmol/L、1 000 nmol/L、10 000 nmol/L）呈剂量依赖性地抑制AngⅡ诱导的HUVEC MCP-1、ICAM-1蛋白和mRNA的表达（P<0.05）,Ang-(1-7) 浓度为1 000 nmol/L时,虽然蛋白和mRNA表达仍高于对照组,但无显著差异（P>0.05）;加入 A-779 组与AngⅡ组比较无显著差异（P>0.05）。结论: Ang-(1-7) 通过其特异性受体MAS拮抗AngⅡ诱导的HUVEC MCP-1和ICAM-1的表达,并呈浓度依赖性。     

血清MCP-1、sTREM-1、sICAM-1在肺炎患儿表达水平及其与病情严重程度的相关性分析

目的探讨血清单核细胞趋化蛋白-1(MCP-1)、可溶性髓细胞触发体-1(sTREM-1)、可溶性细胞间黏附分子-1(sICAM-1)在肺炎患儿表达水平及其与病情严重程度的相关性。方法将我院接诊的108例肺炎患儿纳入肺炎组,分为重症肺炎的重症组(47例)和轻中度肺炎的轻中度组(61例);根据急性生理和慢性健康状况评分(APACHEⅡ),分为高危组(≥20分,32例)、中危组(10~19分,45例)、低危组(<10分,31例),并选取65例健康儿童为对照组,比较各组血清MCP-1、sTREM-1、sICAM-1水平,并分析其与APACHEⅡ评分的相关性。结果在血清MCP-1、sTREM-1、sICAM-1水平比较中,重症组和轻中度组明显高于对照组(P<0.05),重症组明显高于轻中度组(P<0.05),高、中危组明显高于低危组(P<0.05),高危组明显高于中危组(P<0.05),细菌性肺炎组、支原体肺炎组明显高于病毒性肺炎组(P<0.05),细菌性肺炎组明显高于支原体肺炎组(P<0.05);ROC曲线分析显示,sTREM-1的AUC最大,MCP-1的AUC最小;血清MCP-1、sTREM-1、sICAM-1水平与APACHEⅡ评分均呈正相关(P<0.05)。结论血清MCP-1、sTREM-1、sICAM-1水平可反映肺炎患儿的病情严重程度,可作为病情评估的重要指标。     

The intercellular adhesion molecule-1 (ICAM-1) gene polymorphism K469E in end-stage renal disease patients with cardiovascular disease

The intercellular adhesion molecule-1 (ICAM-1) mediates interaction of activated endothelial cells with leukocytes. It plays an important role in the pathogenesis of atherosclerosis. A functionally important polymorphism of the ICAM-1 gene, K469E, has been described. We investigated whether this polymorphism influences the risk of CVD in end-stage renal disease (ESRD) patients. The groups of 1016 ESRD patients and 824 healthy individuals were genotyped by PCR and allele specific oligonucleotide technique. The T allele of the K469E polymorphism was significantly more frequent in ESRD CVD+ patients than CVD- and controls (OR 2.26, 95% CI 1.87-2.72 and 1.82, 95% CI 1.55-2.11, respectively). The TT genotype was also more frequent in CVD+ patients (OR 9.90, 95% CI 6.17-15.88 vs. CVD- subgroup). When patients were stratified according to clinical outcome of CVD, there was a tendency towards higher frequencies of the T allele and TT genotype in patients with myocardial infarction (OR for T allele 1, 57, 95% CI 1.12-2.18 vs. patients without MI). In the multivariate regression analysis the carrier status of T allele of K469E was an independent risk factor of susceptibility to CVD. Our data suggest that the ICAM-1 K469E polymorphism is associated with CVD in ESRD patients.     

血清MCP-1蛋白水平对肺癌及肺结核患者诊断的临床意义

目的 探讨MCP-1蛋白表达在肺癌及肺结核患者中的临床意义。方法 选取2017年1月~2018年12月我院呼吸科收治的40例肺癌及40例肺结核患者为研究对象,同时选取同期在我院体检健康人群40例为对照组,对比三组血清及PBMC上清液中MCP-1浓度及不同期、不同病理类型肺癌患者血清及PBMC上清液中MCP-1浓度和初治和复治肺结核血清及PBMC上清液中MCP-1浓度。结果 肺结核组及肺癌组血清及PBMC上清液中MCP-1浓度高于对照组,且肺结核组高于肺癌组,差异有统计学意义（P＜0.05）;晚期肺癌患者血清及PBMC上清液中MCP-1浓度分别为（152.71±12.56）pg/ml、（419.52±33.93）pg/ml,均高于早期肺癌患者的（73.21±7.90）pg/ml、（312.60±28.62）pg/ml,差异均有统计学意义（P＜0.05）;三种不同病理类型肺癌患者血清及PBMC上清液中MCP-1浓度比较,差异无统计学意义（P＞0.05）;肺结核复治患者血清及PBMC上清液中MCP-1浓度分别为（173.65±13.22）pg/ml、（520.11±67.28）pg/ml,高于肺结核初治患者的（156.21±9.13）pg/ml、（498.34±50.03）pg/ml,差异有统计学意义（P＜0.05）。结论 血清MCP-1蛋白水平于肺癌及肺结核的发生、病情发展有密切的关系,且随病情的进展会升高,临床可将其作为诊治的重要指标。     

Rapid detection of intercellular adhesion molecule 1 (G241R and K469E) polymorphisms by a novel PCR-SSP assay

Intercellular adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein member of the immunoglobulin superfamily and is actively involved in immune and inflammatory responses. We introduce a novel polymerase chain reaction-sequence-specific primers (PCR-SSP) method for rapid and simultaneous genotyping of ICAM-1 G241R and K469E polymorphisms. In a total of 184 DNA samples that have been previously analyzed for these polymorphisms using polymerase chain reaction-restriction fragment length polymorphism technique, re-genotyping of all samples with this new assay showed accurate and reproducible results. As PCR-SSP-based genotyping protocols are more convenient and cost-effective to do, it could therefore offer a valuable tool for assessment of ICAM-1 polymorphisms to which more confirmatory studies are needed.