2型糖尿病血管并发症患者细胞间黏附分子-1基因多态性研究

目的研究细胞间黏附分子-1（ICAM-1）469K〉E基因多态性位点等位基因分布频率及其与2型糖尿病（T2DM）血管病变的关系。方法采用聚合酶链式反应（PCR）方法检测62例T2DM血管并发症患者ICAM-1469KK、KE及EE基因型出现的频率。并检测其空腹血糖（BS）、甘油三酯（TG）、糖化血红蛋白（HbAIc）、血浆游离ICAM-1（sICAM-1）和总胆固醇（TC）水平，并与70例无血管并发症的T2DM患者及121例正常对照组比较。结果KK、KE、EE3种基因型在3组中的分布频率有明显差异（，=6．313，P=0．043）．DM血管病变组等位基因E的频率明显高于对照组和无血管病变组（P〈0．01），T2DM血管病变组ICAM-1469E等位基因携带者sICAM-1水平明显高于K等位基因携带者（P〈0．01）。结论ICAM—1469E等位基因与DM血管病变及ICAM-1水平升高有关。     

细胞间黏附分子-1基因469K/E多态性与心肌梗死的关系探讨

目的探讨细胞间黏附分子-1(ICAM-1)基因K469E多态性与中国汉族人群心肌梗死(MI)发病率的关系.方法采用巢式PCR技术对206例(MI89例)进行ICAM-1基因K469E多态性检测分析.结果基因型频率符合Hardy-Weinberg平衡,MI组和对照组KK、KE、EE基因型频率分别是37.1%、43.8%、19.1%和27.4%、38.5%、34.2%;等位基因K、E频率分别是59.00%、41.00%和46.58%、53.42%,两组差异有统计学意义.回归分析显示,K等位基因、吸烟增加了MI发病的危险,并对MI的发生具有协同作用.结论中国汉族人群存在ICAM-1基因K469E多态性,ICAM-1基因469K/E多态性与MI的发病有关,K等位基因可能为其独立危险因素之一.     

脑梗死患者ICAM-1基因K469E及IL-6基因-174 G/C多态性研究

目的探讨脑梗死与细胞间黏附分子-Ⅰ(ICAM-1)基因K469E多态性及白介素-6(IL-6)基因-174G/C多态性的相关性。方法运用多聚酶链式反应技术(PCR)检测177例脑梗死患者及112例对照者ICAM-1基因K469E多态性及IL-6基因-174G/C多态性各等位基因频率。结果脑梗死患者ICAM-1基因的K469E多态性与对照组比较,KK纯合子频率显著低于对照组(40.7%vs55.4%,P=0.015),KE杂合子频率显著高于对照组(48.6%vs35.7%,P=0.032),E等位基因频率亦显著高于对照组(35.0%vs26.8%,P=0.038),KE和EE基因型与KK基因型的比值比为1.808(95%CI,1.121～2.917)。脑梗死患者组和对照组IL-6基因-174G/C多态性均为GG型纯合子,未检测出C等位基因。结论ICAM-1基因K469E多态性的E等位基因携带者可能患脑梗死的风险增加。     

原发性高血压患者细胞间黏附分子K469E基因多态性与颈动脉内膜中层厚度的相关性研究

目的 探讨ICAM-1基因K496E多态性与动脉粥样硬化(AS)的关系.方法 对437名原发性高血压(EH)患者进行颈动脉超声检测,根据检测结果将所有患者分为AS组和动脉正常组(正常组),采用巢式聚合酶链反应和免疫酶联吸附测定技术检测所有患者的细胞间黏附分子1(ICAM-1)基因K496E基因型和等位基因分布及ICAM-1血浆水平,进行对比分析.结果 AS组KK型频率明显高于正常组(χ2=12.437,P=0.000),基因型相对风险度分析发现,KK基因型的个体发生AS的危险性是KE或EE型的2.087倍(OR=2.087,95%CI=1.382～3.151);携带K等位基因发生AS的风险是E等位基因的1.962倍.经二元多因素Logistic回归分析,调整年龄、性别、体重指数、收缩压、舒张压、总胆固醇、甘油三酯和高密度脂蛋白等指标后,ICAM-1血浆水平、K等位基因和吸烟均不同程度的影响AS的发病,而且K等位基因及吸烟对于AS发病具有一定的协同作用.结论 ICAM-1基因K469E多态性与EH患者的AS有相关性,K等位基因可能是AS的遗传危险因素.     

ICAM-1基因多态性与HBV感染不同临床结局之间的关系

目的探讨细胞间黏附分子l（ICAM-1）基因多态性与HBV感染不同临床结局之间的相关性。方法应用病例．对照研究和聚合酶链反应-序列特异性引物法（PCR-SSP）检测118例慢性持续性HBV感染患者（包括无症状HBV携带者、慢性乙型肝炎、乙肝后肝硬化患者）和60例HBV急性自限性感染者的ICAM-1基因G241R（G／A）、K469E（A／G）两个位点的多态性，比较各组间基因型和等位基因频率，并对数据进行统计分析。结果①ICAM-l G241R（G／A）位点总GG基因型频率在HBV慢性持续性感染组高于急性自限性感染组，但差异无统计学意义（X^2=1．38，P〉0．05）。②ICAM-1 K469E（A／G）位点，进展性肝病组（慢性乙型肝炎和肝硬化）总KK基因型和总K等位基因的频率与无症状携带者组和自限性感染组相比显著增高（X^2=8．60，P〈0．05；X^2=5．07，P〈0、05），而在自限性感染和无症状携带者之间却无显著差异。结论携带ICAM-1 K469E KK基因型和K等位基因的患者容易进展成慢性乙型肝炎甚至肝硬化，可致慢性HBV感染患者病情进展。     

细胞间黏附分子1基因K469E多态性与冠心病的关系

目的 探讨中国河北地区人群中细胞间黏附分子1(ICAM-1)基因第六外显子K469E多态性与冠心病(CHD)的关系.方法 CHD患者93例,同时选取心电图检查无异常或冠状动脉造影正常的101例健康体检者为对照组.所有CHD患者均经冠状动脉造影证实.采用聚合酶链反应-序列特异性引物(PCR-SSP)方法分析CHD患者和对照组的ICAM-1基因型是否有差别.结果 两组基因型频率均符合Hardy-Weinberg遗传平衡.CHD组与对照组ICAM-1基因K469E编码处等位基因频率及基因型频率的差异均无统计学意义.结论 中国河北地区人群中细胞间黏附分子1(ICAM-1)基因K469E多态性与冠心病无相关.     

载脂蛋白H基因多态性与冠心病及血脂代谢关系的研究

目的探讨载脂蛋白H(ApoH)外显子3、8基因多态性与冠心病(CHD)、血脂代谢的关系。方法采用聚合酶链式反应-单链构象多态技术(PCR-SSCP)分析方法,分析了100例健康人及110例CHD患者的ApoH外显子3,8基因型及血脂测定。结果(1)CHD组外显3 GG基因型的频率为81.8%,GA+AA基因型频率为18.2%,G等位基因频率为88%,A等位基因频率是12%,与对照组比较无差异。(2)CHD组外显子8 GG基因型频率为74.5%,GC基因型频率为25.5%,G等位基因频率为87%,C等位基因频率为13%,与对照组比较CHD组的GC基因型频率及C等位基因频率显著增高。(3)外显子3 CHD组低密度胆固醇(LDL-C)高于对照组(P<0.05),CHD组及对照组各基因型间的血脂水平无差异;(4)外显子8 CHD组LDL-C也显著高于对照组(P<0.05),CHD组GC基因型的甘油三酯(TG)显著高于GG型和及对照组的各基因型。结论(1)ApoH外显子3基因多态性与CHD及血脂代谢无相关性;(2)ApoH外显子8 GC基因型及C等位基因与CHD有关,ApoH外显子8基因多态性与TG有关。     

细胞间黏附分子-1基因469K/E多态性与老年冠心病

目的　探讨细胞间黏附分子 1(intercellularadhesionmolecule -1,ICAM- 1)基因4 6 9K/E多态性与老年冠心病患者的关系。方法　利用巢式聚合酶链反应技术,检测12 2例老年冠心病患者(冠心病组)和117例非冠心病住院患者(对照组)的4 6 9K/E突变基因型。结果　基因型频率符合Hardy Weinberg平衡;冠心病组KK +KE基因型频率明显高于EE型,与对照组有显著性差异(P =0 .0 11) ;二元logistic回归显示,K等位基因、吸烟增加了冠心病发病的危险,K等位基因与吸烟对冠心病的发生具有协同作用。结论　ICAM 1基因4 6 9K/E多态性与老年冠心病的发病有关,K等位基因有可能是冠心病发病的遗传危险因素之一     

冠心病患者载脂蛋白A5基因-1131T＞C多态性研究

目的研究载脂蛋白A5基因-1131T>C多态性位点各等位基因分布频率及其与冠心病(CHD)的关系。方法应用聚合酶链反应-限制片长多态性(PCR-RFLP),对210名湖北地区健康汉族人及119名CHD患者基因型进行鉴定,同时对研究对象血脂进行检测。结果CHD组稀有等位基因C携带者TG水平明显高于C非携带者(P<0.01),-1131三种基因型在二组中的分布频率存在显著差异(χ2=7.6,P=0.022),CHD组稀有等位基因C的频率明显高于对照组(χ2=4.66,P=0.031)。结论ApoA5-1131C等位基因与CHD患者TG水平及CHD有关。     

细胞间黏附分子-1基因K469E多态性与缺血性脑血管病的相关性

目的：探讨中国人群中细胞间黏附分子-1（ICAM-1）基因K469E多态性与缺血性脑血管病的相关性.方法：收集112例缺血性脑血管病患者（短暂性脑缺血发作36例,脑梗死76例）和105例对照者,用聚合酶链反应和限制性片段长度多态性分析确定其基因型.结果：病例组ICAM-1 KK基因型频率为0.527,K等位基因频率为0.728,与对照组（分别为0.400和0.610）相比有显著差异（OR=1.71;95%CI 1.14～2.57,P=0.009）.亚组分析表明,短暂性脑缺血发作亚组与对照组之间KK基因型频率无明显差异,而脑梗死亚组与对照组则有明显差异.结论：ICAM-1 469 KK基因型可能是中国人脑梗死的一个独立危险因素.     

Susceptibility to primary sclerosing cholangitis is associated with polymorphisms of intercellular adhesion molecule-1

BACKGROUND/AIMS: Intercellular adhesion molecule-1 (ICAM-1, CD54) gene polymorphisms have been implicated in the susceptibility to a range of inflammatory diseases, including inflammatory bowel disease (IBD). Primary sclerosing cholangitis (PSC) is an immune-mediated chronic cholestatic liver disease associated with IBD. ICAM-1 is expressed on proliferating bile ducts and interlobular bile ducts in late stage PSC and serum levels of soluble intercellular adhesion molecules are increased in PSC. The aim of this study was to analyse ICAM-1 gene polymorphisms in PSC patients. METHODS: In this study, 104 patients with PSC and 213 healthy controls were recruited from Oxfordshire Caucasians. PCR with sequence-specific primers (PCR-SSP) was used to detect both ICAM-1 biallelic polymorphisms G241R and K469E. The results were controlled for the HLA haplotypes associated with PSC. RESULTS: The E/E frequency of K469E in PSC was 12% (12/104), significantly lower than that in controls (24%, 51/213;P = 0.009; Pc = 0.02; OR, 0.41). The occurrence of the haplotype G241-E469/G241-E469 in PSC was 4% (4/104), significantly lower than the control group (13%, 28/213; P = 0.01; Pc = 0.04; OR, 0.26). There was no difference between PSC and control groups in the frequencies of the genotype R241G or in allele frequencies of K469E. CONCLUSIONS: The E469E homozygote status for ICAM-1 is associated with protection against PSC.     

Association of intercellular adhesion molecule 1 polymorphisms with retinopathy in Chinese patients with Type 2 diabetes.

AIMS: To investigate the relationship of the K469E and G241R polymorphisms of the intercellular adhesion molecule 1 (ICAM-1) gene with diabetic retinopathy in Chinese patients with Type 2 diabetes mellitus. PATIENTS AND METHODS: One hundred and seventy-two Chinese patients with Type 2 diabetes and 80 normal control subjects were recruited. Patients with diabetes were placed into two groups: the diabetic retinopathy (DR) group and the non-diabetic retinopathy (NDR) group. The DR group was subdivided into those with proliferative retinopathy (PDR) and non-proliferative retinopathy (NPDR). Genomic DNA was prepared using the hydroxybenzene-chloroform extraction method. Genotypes and alleles were detected by polymerase chain reaction-heteroduplex-single-strand conformation polymorphism (PCR-HA-SSCP) analysis combined with gene sequencing. RESULTS: The patients with retinopathy had an increased frequency of the K469K genotype compared with both the patients without retinopathy and the control subjects (61.4 vs. 40.0 and 35.0%, respectively; chi(2) = 8.280 and 13.952, respectively; P < 0.05). The frequency of the K allele in the DR group was higher than in the NDR group and control subjects (75.4 vs. 58.8 and 61.3%, respectively; chi(2) = 9.693 and 11.219, respectively; P < 0.05). Genotype and allele frequencies were similar in the NDR group and control subjects, and in the PDR and NPDR groups. CONCLUSION: The ICAM-1 gene K469E polymorphism is associated with diabetic retinopathy in Chinese patients with Type 2 diabetes. Patients with the K469K genotype were more likely to have diabetic retinopathy than patients with the K469E or E469E genotype.     

Analysis of MAdCAM-1 and ICAM-1 polymorphisms in 365 Scandinavian patients with primary sclerosing cholangitis

BACKGROUND/AIMS: Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) has been implicated in the aberrant homing of intestinal lymphocytes to the liver in primary sclerosing cholangitis (PSC). Intercellular adhesion molecule-1 (ICAM-1) has also been implicated in the pathogenesis of PSC and the E/E genotype of the K469E polymorphism has been reported to be associated with PSC susceptibility. The aims of this study were to determine if MAdCAM-1 polymorphisms or the K469E polymorphism of ICAM-1 are associated with PSC in Scandinavia. METHODS: Seven single nucleotide polymorphisms (SNPs) in MAdCAM-1 and the G421R and K469E ICAM-1 SNPs were genotyped in 365 PSC patients from Norway and Sweden. 327 Norwegian ulcerative colitis (UC) patients and 368 Norwegian bone marrow donors served as controls. RESULTS: No significant association with PSC was found for any of the MAdCAM-1 or ICAM-1 SNPs. Allele frequencies for these polymorphisms were not significantly different between PSC patients with UC, UC patients and healthy controls. CONCLUSIONS: Polymorphisms in MAdCAM-1 are not likely to significantly affect PSC susceptibility. In addition, the E/E genotype of the K469E in ICAM-1 does not influence PSC susceptibility in Scandinavia.     

Intercellular adhesion molecule 1 gene polymorphisms do not contribute to Graves' disease in Chinese patients

Objective In order to study the association of G241R polymorphism of ICAM-1 gene with an earlier onset of Graves’ disease (GD) and the susceptibility of K469E polymorphism to Graves’ ophthalmopathy (GO) in Chinese population. Study Design A case-control and replication study was performed in 212 GD patients and 204 healthy subjects to analyze the genotypes. Furthermore the distribution of ICAM-1 genotypes was investigated in subgroups of patients with GD according to the onset age and the ophthalmopathy. Results No G241R polymorphism of ICAM-1 gene was detected in Chinese. No significant differences of allele and genotype frequencies regarding K469E polymorphism were found between GD patients and healthy controls (χ2 = 0.092, P = 0.762; χ2 = 1.089, P = 0.580). In addition, the genotype–phenotype correlation was not identified either. Conclusions We found no association of G241R and K469E polymorphisms of the ICAM-1gene with the development of GD in a Chinese population. However, we could not rule out possible contributions of other polymorphisms of the ICAM-1gene to the pathogenesis of GD. Therefore, further studies are needed to elucidate the role of ICAM-1gene in Graves’ disease in different population. Shu Wang and Hua Sun contributed equally to this work.     

Susceptibility to active decompensated cirrhosis is associated with polymorphisms of intercellular adhesion molecule-1 (ICAM-1) in chronic HBV carriers

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the pathogenesis of viral hepatitis B. Several inflammatory diseases are associated with distinct polymorphisms of the ICAM-1 gene. The aims of this study were to analyse the association of ICAM-1 polymorphisms G241R and K469E with susceptibility to active decompensated cirrhosis in chronic hepatitis B virus (HBV) carriers. The polymorphisms at codons G241R and K469E of ICAM-1 were analysed by sequence-specific primer polymerase chain reaction (PCR-SSP) in 572 unrelated chronic HBV carriers and 157 unrelated healthy HBV non-infected blood donors. There were significantly increased frequencies of R at codon 241 and E at codon 469 in patients with active decompensated cirrhosis (38.3% and 58.3%), compared with patients with chronic hepatitis B (CHB; 21.9% and 46.5%) and chronic asymptomatic HBV carriers (AsC; 12.6% and 40.3%). The frequencies of R241-E469 haplotype and genotypes carrying at least one R241-E469 haplotype were significantly higher in patients with active decompensated cirrhosis than those in patients with CHB (38.3% and 63.3%vs 21.9% and 36.7%), and significantly higher in patients with CHB than those in AsC (21.9% and 36.7%vs 12.6% and 23.3%). The ICAM-1 polymorphisms at codons G241R and E469K were associated with the disease susceptibility, and susceptibility to active decompensated cirrhosis is significantly increased in chronic HBV carriers carrying at least one R241-E469 haplotype.     

Intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in Italian patients with rheumatoid arthritis

AIMS: Rheumatoid arthritis (RA) has a wide range of clinical expressions which probably reflects different genetic backgrounds. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory synovial activity in RA. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with RA and its severity. METHODS: Seventy-eight seropositive Italian RA patients with erosive disease entered the study. Radiographs of hands and feet 5 years after the diagnosis were available for 68 patients and were evaluated for the number of eroded joints. We obtained an erosive score for each patient by counting the number of joints with at least one erosion. Patients in the upper part of the distribution over the median were considered as fast eroders (FE) and the others as slow eroders (SE). Patients' records were also evaluated for the presence of extra-articular features. 228 healthy subjects of the same ethnic origin were selected as a control group. All of the RA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 (exon 4) and E/K at codon 469 (exon 6). RESULTS: The carriage rate of allele R241 was significantly higher in RA patients than in healthy controls (12.8% versus 5.7%, p = 0.039; odds ratio: 2.4 [95% CI 1.02 to 5.79]). The allele frequencies and carriage rate of the E 469 gene did not differ significantly between RA patients and the control group. When we compared the control group with the patients with more or less severe disease (presence or absence of extra-articular features, SE and FE) we found that only the group of patients with the more favourable course maintained a significant difference in the carriage rate of R241 (16.7 vs 5.7%, p = 0.009 for patients without extra-articular features and 18.9 vs 5.7%, p = 0.004 for SE patients). CONCLUSION: Our preliminary findings show that G/R 241 polymorphism of ICAM-1 is associated with RA, and that this confers a reduced risk of extra-articular manifestations and is associated with a slow rate of joint destruction.     

Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population

BACKGROUND AND AIMS: The genetic contribution to inflammatory bowel disease (IBD) is under investigation. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and IBD. We investigated the association between an intercellular adhesion molecule 1 gene (ICAM-1) polymorphism located on chromosome 19p13 and IBD in a Japanese population. METHODS: We compared 207 Japanese patients who had IBD (79 with Crohn's disease (CD); 128 with ulcerative colitis (UC)) with 103 unrelated Japanese controls. We determined R241G and K469E polymorphisms of the ICAM-1 gene using polymerase chain reaction (PCR) techniques. RESULTS: Both frequency and carriage rate of the K469 allele were significantly higher in IBD patients than in controls (allelic frequency, p(c)=0.0026; carriage rate, p(c)=0.0034; odds ratio 2.59; 95% confidence interval 1.42-4.68). Furthermore, the frequency of the K469 allele was significantly increased in both CD and UC. Subgroup analysis demonstrated that both K469 allelic frequency and K469 carriage rate were significantly higher in patients with the small bowel and colon type of CD and entire colitis compared with healthy controls. CONCLUSIONS: We identified an overall association between IBD and ICAM-1 K469 in a Japanese population. Further studies of this chromosome region are required to elucidate the gene responsible for IBD.     

Polymorphism at codon 469 of the intercellular adhesion molecule-1 locus is associated with protection against severe gastrointestinal complications in Henoch-Schönlein purpura

OBJECTIVE: Henoch-Schonlein purpura (HSP) is a small sized vasculitis affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have recently been implicated in the susceptibility to some vasculitides. To further investigate the clinical implication of ICAM-1 polymorphisms in HSP, we examined their potential association and influence in the development of severe complications in an unselected series of patients with HSP. METHODS: Fifty-two patients, of which 41 were children, were diagnosed with HSP using classification criteria of Michel, et al at the Hospital Xeral-Calde (Lugo, Spain); 129 ethnically matched controls were included. Patients had at least one year of followup. Patients and controls were genotyped by allelic oligonucleotide techniques for ICAM-I polymorphism at codon 241 and 469. RESULTS: The frequency distribution of the alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between HSP patients and controls. Also, no differences between patients with or without renal manifestations were found. However, the frequency of the codon 469 K/E genotype was significantly decreased in patients without severe gastrointestinal manifestations compared to those with them (22.29 vs 65%, OR 0.1, p = 0.02, after correction for age, sex, and disease duration). None of the 11 adults exhibited the R/G genotype at codon 241 compared with 7 of 41 children (OR 0.0, 95% CI 0.0-2.9, p = 0.14). Patients with the R/G genotype were associated with low incidence of renal manifestations and none developed permanent renal involvement (renal sequelae); however, this finding did not achieve statistical significance. CONCLUSION: ICAM-1 polymorphisms alone are not associated with development of HSP, but patients not carrying the codon 469 K/E genotype are at decreased risk of developing severe gastrointestinal complications. The R/G polymorphism at codon 241 may reduce the risk of renal sequelae in the development of HSP in adulthood.     

Intercellular adhesion molecule-1 gene polymorphisms in Beh?et's Disease.

OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Beh?et's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility. METHODS: Case patients were 74 consecutive Italian patients with BD who were followed at the Bologna, Ferrara, Milano, Potenza, Prato, Reggio Emilia, and Trento rheumatology, ophthalmology, and neurology units over a 3 year period (1997-99) who satisfied the International Study Group criteria for BD; 228 healthy Italian blood donors from the same geographic areas were selected as control groups. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in BD patients than in controls (20.3% vs 5.7%; p = 0.001, pcorr = 0.002, OR 4.2, 95% CI 1.9-9.3). The distribution of E/K 469 genotype was similar in patients and controls. Comparing patients with different clinical features, we found only a trend to higher frequency of R241 in patients with articular manifestations (21.4% vs 12.5%; p = 0.08). CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with BD susceptibility.