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。     

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.     

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。     

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。     

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.     

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。     

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.     

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.     

Intercellular adhesion molecule-1 polymorphisms in Korean patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by synovial proliferation and the accumulation of inflammatory cells in the affected joints. Intercellular adhesion molecule-1 (ICAM-1) is readily detected in RA synovial tissues and helps recruit inflammatory cells to the joint. ICAM-1 shows genetic polymorphisms at codons 241 (R241G) and 469 (K469E). In order to investigate the association between ICAM-1 gene polymorphisms and RA, we genotyped ICAM-1 R241G and ICAM-1 K469E polymorphisms in 143 Korean patients with RA, and in 138 healthy controls, by using the polymerase chain reaction-restriction fragment length polymorphism method. No polymorphism of R241G was found in Korean subjects. However, the frequency of the K469 allele was found to be significantly lower in RA patients than in healthy controls. Allele frequency of K469 was lower in RA patient group, compared to that in healthy controls, regardless of the shared epitope status. Distribution of K469E allele frequencies was not different whether the patient had rheumatoid factor, radiographic erosion or extra-articular complications. In conclusion, this study shows lower frequency of the ICAM-1 K469E allele in Korean patients with RA than that in healthy controls.     

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 (ICAM-1) gene polymorphisms in endometriosis

Endometriosis is a gynaecological disease with a certain genetic background, but the locations of possible genomic aberrations are still poorly clarified. Intercellular adhesion molecule-1 (ICAM-1), which is a surface glycoprotein that promotes adhesion in immunological and inflammatory reactions, seems to play a role in this condition. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with endometriosis and its severity. Specifically, we have studied two polymorphic sites located in codons 241 (G/R241) and 469 (E/K469) of the ICAM-1 gene. Three hundred and sixty-three Italian Caucasian women of reproductive age who underwent laparoscopy for benign pelvic conditions were enrolled in the study. Endometriosis was documented and staged in 188 women while 175 subjects, in whom endometriosis was laparoscopically ruled out, served as the control group. The frequency of the R241 allele was only marginally higher in endometriosis patients than in controls [5.8 versus 2.9%, P = 0.05; odds ratio (OR), 2.1; 95% confidence interval (CI), 1-4.5]. However, a strikingly high frequency of this allele was found in patients with Stage IV endometriosis versus controls (8.6 versus 2.8%, P = 0.008; OR, 3.2; 95% CI, 1.3-7.9). In contrast, the allele and genotype frequencies of the E/K469 polymorphism did not differ significantly between endometriosis and control groups. While the functional correlate of the G/R241 polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain may contribute to the susceptibility to endometriosis.     

The Polymorphisms K469E and G261R of Intercellular Adhesion Molecule-1 and Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

Objective: The aim of this study was to explore whether polymorphisms of intercellular adhesion molecule-1 (ICAM-1) are associated with susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC).

Methods: The authors conducted a meta-analysis on the associations between the polymorphisms K469E and G241R of ICAM-1 and susceptibility to CD and UC.

Results: A total of 8 studies with 801 patients with CD, 672 patients with UC, and 1,828 controls were included in the meta-analysis. The meta-analysis revealed no association between CD and the ICAM-1 469E allele among the subjects (OR?=?1.175, 95% CI?=?0.901–1.533, p?=?0.233). However, stratification by ethnicity indicated an association between the ICAM-1 469E allele and CD in Europeans (OR?=?1.425, 95% CI?=?1.013–2.002, p?=?0.042). Meta-analysis using the homozygosity also showed an association with CD in Europeans (OR?=?2.054, 95% CI?=?1.036–4.073, p?=?0.039). The meta-analysis revealed no association between UC and the ICAM-1 K469E polymorphism. No association between CD or UC and the ICAM-1 G241R polymorphism was observed.

Conclusions: This meta-analysis demonstrates that the ICAM-1 K469E polymorphism may be associated with susceptibility to CD in Europeans, but no association was found between ICAM-1 K469E and UC. In contrast, the G241R polymorphism was not found to be associated with susceptibility to either CD or UC.