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。     

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。     

转化生长因子β1基因869T/C、915G/C多态性与食管癌关系的研究

目的研究转化生长因子β1(TGF-β1)第1外显子+869T/C、+915G/C基因多态性与广西地区食管癌的关系。方法采用序列特异性引物聚合酶链反应(PCR-SSP)技术,检测118例食管癌患者和130例正常对照组TGF-β1的基因多态性,同时采用酶联免疫吸附试验(ELISA)检测血清TGF-β1水平。结果食管癌患者血清TGF-β1水平显著高于对照组(P<0.01),TGF-β1基因+915G/C多态性各等位基因及基因型频率在两组人群中的分布差异有统计学意义(P<0.05),等位基因频率的相对风险分析发现,C等位基因携带者患食管癌的风险是G等位基因的3.077倍(OR=3.077,95%CI1.336~7.087),携带C等位基因食管癌患者血清TGF-β1水平显著高于不携带者[(55.37±9.76)μg/Lvs(48.29±8.29)μg/L,P<0.05];而TGF-β1基因+869T/C多态性在食管癌组和正常人群中的分布差异无统计学意义(P>0.05)。结论TGF-β1基因+915G/C多态性与食管癌的发病具有相关性,其中C等位基因可能是食管癌发病的遗传易感基因;携带C等位基因的个体可能通过促进TGF-β1的高度表达进而增加了食管癌的发病风险。     

白细胞介素-1基因多态性与原发性高血压关联

目的研究白细胞介素-1(IL-1)基因多态性与原发性高血压的相关关系。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150例原发性高血压患者和160例健康对照者IL-1基因多态性。结果IL-1α基因-889C/T多态性在两组人群中的分布差异显著(P<0.05);等位基因频率的相对风险分析发现,T等位基因携带者患原发性高血压的风险是C等位基因的2.102倍(OR=2.102,95%CI:1.231~3.590),携带CT+TT基因型的原发性高血压患者收缩压水平显著高于CC基因型者[(168.9±19.8)mmHg比较(160.2±18.9)mmHg],(P<0.05)。结论IL-1α基因-889C/T多态性与原发性高血压的发病具有相关性,其中T等位基因可能是原发性高血压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收缩压的升高进而增加了原发性高血压的发病风险。     

TGF-β1基因启动子-800G/A、-509C/T多态性与食管癌的研究

目的研究转化生长因子β1(TGF-β1)基因启动子多态性各等位基因及基因型在食管癌患者中的分布频率,初步分析其基因型及血清水平与食管癌的相关性.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118例食管癌患者和130例正常对照组TGF-β1的基因多态性,包括TGF-β1基因启动子-800G/A、-509C/T位点,同时采用ELISA检测血清TGF-β1水平.结果食管癌患者血清TGF-β1水平显著高于对照组(P＜0.01),TGF-β1基因-800G/A位点多态性在食管癌组和正常人群中的分布差异无显著性(P＞0.05),而TGF-β1基因-509C/T多态性各等位基因及基因型频率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等位基因携带者患食管癌的风险是C等位基因的1.624倍(OR=1.624,95%CI1.134～2.324),携带T等位基因的食管癌患者血清TGF-β1水平显著高于不携带者(50.97±8.91μg/LVS44.23±8.54μg/L,P＜0.01).结论TGF-β1基因-509C/T多态性与食管癌的发病具有相关性,其中T等位基因可能是食管癌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TGF-β1的高度表达进而增加了食管癌的发病风险.     

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.     

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.     

新疆维吾尔族阿尔茨海默病患者脑啡肽酶基因与载脂蛋白E基因多态性的关联分析

目的 探讨脑啡肽酶(neprilysin,NEP)基因rs3736187位点突变及其与载脂蛋白E(apolipoprotein E,ApoE)基因相互作用在新疆维吾尔族人群散发性阿尔茨海默病(sporadic Alzheimer disease,SAD)发病机制中的作用.方法 应用聚合酶链反应-限制性片段长度多态性方法 检测了111例维吾尔族SAD患者和117名维吾尔族正常老年人NEP基因和ApoE基因多态性分布特征.结果 (1)NEP基因T等位基因频率在AD组高于对照组(x2=5.005,P＜0.05),携带T等位基因个体出现AD的危险性高于携带C等位基因的个体.(2)ApoE基因ε4等位基因频率AD组高于对照组(x2=4.218,P＜0.05),携带ε4等位基因个体出现AD的危险性高于未携带ε4等位基因的个体.(3)NEP基因的T等位基因与SAD发病相关且不受ApoE基因型影响.结论 NEP基因和ApoE基因的基因多态性与新疆维吾尔族SAD发病有关联.NEP基因可能是新疆维吾尔族SAD发病独立的易感基因.     

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。     

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.     

Intercellular adhesion molecule 1 K469E gene polymorphism is associated with presence of skin lesions in Tunisian Behçet's disease patients

Abstract
Intercellular adhesion molecule 1 ( ICAM1 ) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases. The expression of both soluble and tissue ICAM1 were increased in Behçet's disease (BD) but the contribution of ICAM1 gene polymorphisms to this disease remains unknown. We sought to establish the association of ICAM1 gene K469E polymorphism in exon 6 with susceptibility for BD. One hundred and thirty-five Tunisian patients who satisfied the International Study Group criteria for BD and 157 healthy blood donor controls from the same geographic area were genotyped by polymerase chain reaction method for the K469E ICAM1 gene polymorphisms in exon 6. There were no significant differences in the distribution of the K469E allele or genotype frequencies between the BD patients and healthy controls in the ICA1 gene. Among patients, significant association was found between the presence of skin lesions and the studied polymorphism in the distribution of the K469E allele ( P = 0.004; odds ratio = 1.26; 95% confidence interval = 2.13–3.62) and genotype frequencies ( P = 0.0028;χ² = 11.75). Our findings suggest that K469E ICAM1 gene polymorphism was associated with Tunisian BD patients with skin lesions.     

The intercellular adhesion molecule‐1 (ICAM‐1) gene K469E polymorphism is not associated with ischaemic heart disease: an investigation using family‐based tests of association

The possible role of the K469E polymorphism in the intercellular adhesion molecule‐1 (ICAM‐1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well‐defined Irish population using two recently described family‐based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the ICAM‐1 K469E polymorphism. Using the combined transmission disequilibrium test (TDT)/sib‐TDT and the pedigree disequilibrium test (PDT), no association between the ICAM‐1 K469E polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the ICAM‐1 K469E polymorphism is not associated with IHD.     

Absence of association between an intercellular adhesion molecule 1 gene E469K polymorphism and Alzheimer's disease in Finnish patients

Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein known to contribute to inflammatory responses, has been detected in the brain tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis of these disorders. Our purpose was to investigate whether genetic variants of the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control patients of Finnish origin. The distributions of the genotype and allele frequencies of the polymorphism did not differ significantly between the AD, PD or the control patients. We therefore conclude that the E469K polymorphism of ICAM1 is not a risk factor for AD or PD.     

ICAM1 amino-acid variant K469E is associated with paediatric bronchial asthma and elevated sICAM1 levels

Intercellular adhesion molecule-1 (ICAM1) acts as ligand for beta2-integrin molecules and mediates leucocyte trafficking to the site of inflammation. Intercellular adhesion molecule-1-deficient mice show impaired lymphocyte recruitment to the lung, less airway hyper-responsiveness and less lung inflammation than healthy controls. Thus, the aim of the study was to test common ICAM1 polymorphisms for association with paediatric asthma. Furthermore, we were interested in whether soluble ICAM1 (sICAM1) serum levels were in correlation with genotypes. The following polymorphisms in ICAM1 were genotyped on 352 children with asthma and 270 controls: rs5491 (resulting in the amino-acid exchange K56M), rs5493 (G241S), rs5498 (K469E), rs5030400 (R478W) and rs885743 in the 3'-untranslated region. In addition, sICAM1 serum levels were measured. Only K469E and rs885743 were present in our populations. K469E showed association with asthma (P = 0.0037 with Armitage's trend test). Haplotype analysis by FAMHAP using both polymorphisms revealed association with asthma by P < 0.000001. In addition, serum sICAM1 levels were correlated with K469E genotypes (P = 0.009 by Kruskal-Wallis test). We conclude from our data that K469KE is associated with paediatric asthma in the German population. Furthermore, the same polymorphism is correlated with serum levels of sICAM1. Functional analyses have to further clarify the pathophysiological mechanism conferred by the polymorphisms.     

广西壮族人群ABCA1基因R219K和I883M多态性的分布

目的探讨ABCA1基因R219K和I883M多态性在广西壮族人群中的分布。方法采用PCR-RFLP技术对100例无血缘关系的健康壮族人的ABCA1基因R219K位点G→A(Arg219Lys)和I883M位点A→G(Ile883Met)进行检测,121例无血缘关系的健康汉族人做对照。结果在广西壮族人群中ABCA1基因R219K等位基因频率分别为R=0.640和K=0.360,I883M等位基因频率分别为I=0.305和M=0.695,壮族883I等位基因频率和II纯合子基因型频率明显高于汉族,但R219K和I883M多态分布在壮族和汉族人群间的差异均无统计学意义(P>0.05)。而两个位点分布与德国人群相比,差异有统计学意义(P<0.05)。结论ABCA1基因R219K及I883M位点多态性在广西壮族与汉族的分布没有差异,而有别于西方人种,提示该基因多态性具有种族差异性。该数据可以很好地应用于群体遗传学以及其与脂代谢疾病易感性的研究。     

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.