急性心肌梗死患者白细胞介素-6血清水平及其基因多态性研究

目的探讨急性心肌梗死(AMI)患者白细胞介素-6(IL-6)血清水平和IL-6基因-572C/G多态性在中国汉族人群中的分布频率及其与AMI易感性的关系。方法对145例AMI患者和170名健康对照人群进行IL-6血清水平和基因-572C/G多态性检测,IL-6血清水平采用ELISA法测定,基因型检测应用PCR/RFLP方法。结果AMI患者血清IL-6水平显著高于对照组[(25.36±19.91)pg/ml比(4.59±2.69)pg/ml,P<0.01]。AMI组CC、CG、GG三种基因型频率为52.41%、41.38%、6.21%;对照组为64.12%、34.70%、1.18%。两组间基因型、等位基因频率比较有显著性差异,前者CG GG基因型频率与G等位基因频率均显著高于后者(P均<0.05)。CG GG基因型人群患AMI的风险是CC基因型人群的1.62倍(95%CI:1.03~2.55,P<0.05)。不同基因型人群间血清IL-6水平无差异。结论AMI患者血清IL-6水平高,-572CG GG基因型频率高,IL-6基因-572G等位基因可能是中国汉族人群AMI发生的易感基因之一。     

白细胞介素-6基因多态性对冠心病发病易感性的影响及其机制

目的了解白细胞介素-6（IL-6）基因-597G／A及-572C／G多态性对冠心病（CHD）发病易感性的影响及其影响机制。方法 应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）分析方法,测定245例CHD患者和260例正常对照者的IL-6基因型,探讨其与CHD的相关关系;观察基因型对血清IL-6水平的影响,并采用logistic回归分析法了解基因型与CHD其他危险因素间的相互作用。结果 两组研究对象中-597位点均仅发现GG基因型。-572C／G基因型和等位基因频率在两组间存在明显统计学差异（P均〈0．01）,CHD组GG基因型和G等位基因频率均显著高于对照组（P均〈0．01）;CG、GG基因型人群患CHD的风险分别为CC基因型人群的1．46倍（95％CI：1．01～2．10,P〈0．05）和5．19倍（95％CI：1．69～15．89,P〈0．01）;不同基因型患者间血清IL-6水平无统计学差异（P〉0．05）;-572C／G基因型与总胆固醇、甘油三酯间存在一定的交互作用,OR值分别为1．76（95％CI：1．05～3．16,P〈0．05）、2．51（95％CI：1．04～6．45,P〈0．05）。结论 IL-6基因-597G／A多态性可能与中国汉族人群CHD发病易感性无关,而-572C／G多态性可能是该人群CHD发病的易感基因之一,其可能通过对组织IL-6水平的影响及与血脂的协同作用参与CHD的发生。     

唐山地区汉族人群白细胞介素6基因-572C/G多态性与脑梗死关系的研究

目的探讨唐山地区汉族部分人群白细胞介素6(IL-6)基因-572C/G多态性与脑梗死的关系。方法采用多聚酶链反应-限制性片段长度多态性,检测118例首次新发脑梗死患者(脑梗死组)和154例健康体检者(对照组)IL-6基因-572C/G多态性位点频率,分析基因型与脑梗死的相关性。结果脑梗死组患者-572位点CC、CG、GG基因型频率分别为50.85%、41.53%、7.63%;对照组CC、CG、GG基因型频率分别为65.58%、31.82%、2.60%。脑梗死组和对照组-572位点C等位基因频率分别为71.61%、81.49%;G等位基因频率分别为28.39%、18.51%,差异有统计学意义(P0.05)。CG、GG基因型人群患脑梗死的风险分别是CC基因型的1.683倍(95% CI:1.012～2.800,P0.05)和3.788倍(95% CI:1.11 8～12.833,P0.05)。多因素logistic回归分析显示,-572G等位基因是脑梗死发生的独立危险因素。结论唐山地区汉族部分人群中存在IL-6基因-572C/G多态性,可能与脑梗死有关,-572G等位基因可能是脑梗死发病的易感基因。     

白细胞介素6基因-597G/A与-572C/G多态性对心房颤动发病易感性的影响

目的 了解白细胞介素6(IL-6)基因-597G/A及-572C/G多态性对心房颤动(房颤)发病易感性的影响.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,测定291例房颤患者(房颤组)和325例正常对照者(对照组)的IL-6基因-597G/A及-572C/G多态性,探讨其与房颤的相关关系、对不同病因及不同临床类型房颤的影响,观察其对左心房内径(LAD)、血清IL-6水平及外周血单个核细胞(PBMC)产生IL-6能力的影响.结果 在研究人群中,-597位点仅发现有GG基因型.-572位点存在3种基因型,房颤组CG+GG基因型和G等位基因频率分别为51.55％和29.90％,与对照组相比差异有统计学意义(P＜0.001),对照组中分别为35.38％、18.77％;G等位基因携带者患房颤的风险是CC基因型的1.94倍(95％ CI:1.41～2.68,P＜0.001);校正了其他因素的影响后,CG+GG基因型仍然是房颤发生的独立危险因素(OR=1.63,95％ CI:1.05～2.51,P＜0.05).孤立性、高血压、冠心病等不同病因以及不同临床类型房颤间-572C/G多态性分布差异无统计学意义(P＞0.05).房颤组CG+GG基因型人群LAD值高于CC基因型人群[(37.51±8.78)mm对(35.26±5.52) mm,P＜0.05].不同基因型人群血清IL-6水平差异无统计学意义(P＞0.05),但对照组G等位基因携带者PBMC随培养时间的延长上清液IL-6含量高于CC基因型人群(P＜0.05).结论 IL-6基因-597G/A多态性可能与中国汉族人群房颤发病易感性无关;而-572C/G多态性可能是该人群房颤发病的易感基因之一,该多态性存在一定的功能.     

白细胞介素-6基因多态性与慢性阻塞性肺疾病及吸烟因素的相关性研究

目的 探讨白细胞介素（IL）-6启动子区域基因-572C/G单核苷酸多态性与慢性阻塞性肺疾病（COPD）易感性及吸烟因素之间的关系.方法 应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法,检测并分析COPD患者和健康对照者IL-6-572C/G位点基因型分布情况,同时分析该多态性位点与吸烟相关COPD之间是否存在相关性.结果 中国上海地区汉族人群存在IL-6基因-572C/G多态性;COPD组CG、GG基因型、G等位基因频率均高于对照组（P＜0.01）;基因型频率的相对风险分析发现,CG、GG基因型各自患COPD的风险分别是CC基因型的2.09倍（95％ CI：1.03 ～4.23）和5.44倍（95％ CI：1.20 ～ 24.75）;-572C/G多态性在轻中度、重度COPD组间的分布比较差异无统计学意义;该突变位点与吸烟所致的COPD之间无相关性存在.结论 IL-6基因-572G等位基因可能是中国汉族人COPD发生的易感因子,可能与携带该等位基因的人群存在IL-6水平高表达有关,其基因分布与吸烟相关的COPD无明显相关.     

冠心病与白细胞介素6基因-572C/G多态性的相关性

为了解冠心病与白细胞介素6基因-572C/G多态的相关关系,应用聚合酶链反应-限制性片长多态性分析方法测定了139例冠心病患者和168例正常对照者的白细胞介素6基因-572C/G多态性,并结合疾病临床谱、冠状动脉造影结果探讨了其与冠心病的相关关系.结果发现,-572C/G基因型和等位基因频率在两组间存在明显差异,冠心病组GG基因型和G等位基因频率均显著高于对照组(P<0.01);相对于CC基因型,暴露于CG基因型、GG基因型的相对危险度分别为1.37(95%CI 0.86～2.20,P>0.05)和2.85(95%CI1.32～6.13,P<0.01),校正了血压、血糖和血脂等传统危险因素的影响后,GG基因型的相对危险度(95%CI 1.22～6.65, P<0.05)仍然具有统计学意义;但-572C/G多态性在稳定型心绞痛、不稳定型心绞痛、心肌梗死患者间以及在单支病变组、双支病变组、三支病变组间的分布均无明显差异(P>0.05).结果提示,白细胞介素6基因-572GG基因型可能是中国汉族人群冠心病发病的易感基因之一.     

辽宁地区健康汉族人IL-6基因-572C/G多态性观察

目的观察辽宁地区健康汉族人群中白细胞介素-6（IL-6）基因-572C/G多态性。方法选择辽宁地区366例健康汉族人,采用聚合酶链反应—限制性片段长度多态性技术检测其血清中IL-6基因的-572C/G多态性。结果辽宁地区健康汉族人IL-6基因-572C/G基因型中CC、CG、GG型频率分别为63.93%、34.15%、1.92%。C等位基因与G等位基因频率分别为81.01%、18.99%。结论辽宁地区健康汉族人IL-6基因在-572C/G存多态性,其中CC纯合子最多见,CG杂合子次之,GG纯合子最少见;C等位基因为常见基因,G等位基因为少见基因。     

IL-6基因启动子区-174C/G、-572C/G位点单核苷酸多态性与大动脉炎易感性之间的联系

目的大动脉炎(takayasu arteritis, TA)是一种主要累及大动脉及其一级分支的慢性炎症,目前TA的发病机制尚不明确,认为其发生发展与多种因素相关。白细胞介素6(interleukin 6, IL-6)与多种炎症性及免疫性疾病相关,既往研究提示IL-6启动区基因多态性可能与TA易感性相关,本研究将探讨IL-6基因启动子区-174C/G和-572C/G多态性与TA易感性之间的关联。方法纳入2011年12月～2014年1月在阜外医院确诊的111例大动脉炎患者(TA组),并选取197名健康的汉族人作为对照(对照组),描述并比较两组患者-174C/G(rs1800795)和-572C/G(rs1800796)位点的等位基因频率和基因型分布情况。结果 IL-6基因启动子区-174C/G位点基因型分别CC型和CG型,-572C/G位点检测到CC、CG和GG三种基因型,且-174C/G和-572C/G等位基因和基因型频率符合哈迪-温伯格遗传平衡。IL-6-174C/G位点CC基因型的分布频率在患者组和对照组中分别为97.3%,98.5%,CG基因型分布频率分别为2.7%,1.5%;IL-6-572C/G位点CC、CG、GG基因型在患者组的分布频率分别为44.2%,48.6%,7.2%,对照组分别为45.2%、47.7%、7.1%;两个位点基因型在TA组和对照组间分布差异无统计学意义(P值分别为0.47,0.86,0.94)。-174C/G位点CC基因型与CG基因型比值比分别为1.00和0.55,P=0.47;-572C/G位点CC、CG、GG基因型比值比分别为1.00,1.04和1.03。在显性遗传模式下,-572C/G位点CC与CG+GG基因型的比值比分别为1.00和0.96;隐性遗传模式下,-572C/G位点CC+CG与GG基因型的比值比分别为1.00和1.03;共显性遗传模式下,-572C/G位点CC、CG与GG基因型的比值比分别为1.00,1.04和1.03,三种遗传模型下基因型分布在两组之间无明显差异。-174C/G和-572C/G形成的单倍型在两组研究对象中分布差异无统计学意义(P=0.83)。结论 TA患者中IL-6基因启动子区-174C/G和-572C/G位点等位基因频率、基因型分布和基因型组合分布与正常人无差异,因此汉族人群中-174C/G和-572C/G基因单核酸多态性与大动脉炎易感性无关。     

IL-6基因多态性与乙型肝炎慢性化的相关性

目的探讨汉族成人IL-6基因多态现象与乙型肝炎慢性化的关系。方法收集118例慢性乙型肝炎(CHB)患者和61例急性乙型肝炎(AHB)患者外周血,提取基因组DNA;采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)分析方法进行IL-6-572C/G和-597G/A基因分型。结果 CHB组IL-6-572G等位基因频率显著高于AHB组(χ2=8.627,P=0.003)。与CC基因型相比,CG和GG基因型携带者发生慢性化的危险性升高(ORCG=2.024,95%CI:1.009～4.065;ORGG=3.367,95%CI:1.169～9.709)。结论 IL-6-572基因位点多态性与乙型肝炎慢性化有关,携带-572GG基因型的乙型肝炎患者易发生慢性化。     

中国人白细胞介素-6基因多态性与动脉粥样硬化相关性的Meta分析

目的分析白细胞介素(IL)-6基因多态性与中国居民动脉粥样硬化(AS)发病风险的相关性。方法按照综合的检索策略在万方、CNKI、维普、Pubmed和Web of Science数据库中全面检索关于IL-6基因多态性与AS相关性的病例对照研究,应用Stata11.0进行Meta分析。结果最终15篇相关文献符合纳入排除标准。经过Meta分析,发现IL-6-174G/C多态性与AS无关;IL-6-572C/G多态性与AS显著相关:携带GC基因型个体患AS的危险性是CC基因型个体的1.68倍(95%CI=1.47~1.93,P<0.001);携带GG基因型个体患AS的危险性是CC基因型个体的2.45倍(95%CI=1.78~3.37,P<0.001)。结论 IL-6-572C/G多态GC和GG基因型是AS发生的风险基因型。     

The endothelial dysfunction in patients with type 2 diabetes mellitus is associated with IL-6 gene promoter polymorphism in Chinese population

The purpose of this study is to examine the effects of IL-6 gene promoter -174G/C and -572G/C polymorphism on endothelial function of Chinese T2DM and normal glucose regulation (NGR) subjects. 512 newly diagnosed T2DM patients and 483 NGR subjects were recruited and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed for the IL-6 gene promoter -174G/C and -572G/C polymorphism. Flow-mediated dilation (FMD) was measured as a non-invasive indicator for endothelial function. The results show that the C allele and CC genotype at -174 of IL-6 gene promoter region was extremely rare in both T2DM and NGR groups; genotypes' and alleles' frequency at -572 of IL-6 gene promoter region is of no difference between T2DM and NGR groups; within T2DM group, higher plasma IL-6 concentration and lower FMD was found in patients with -572 GC (2.36 ± 0.69, 4.23 ± 3.82%) or GG (2.32 ± 0.74, 4.24 ± 3.67%) genotype, compared with patients with CC (2.15 ± 0.62, 5.28 ± 3.94%) genotype. The conclusion of the study is that in comparison with patients of CC genotype, the T2DM patients of -572 GC or GG genotype may have more aggravated endothelial dysfunction (ED) and be at higher risk for coronary artery disease (CAD).     

急慢性HBV感染者外周血白细胞IL-6-572位点基因多态性分析

目的探讨成年人群IL-6基因启动子区-597G/A和-572C/G位点多态性与HBV感染的关系。方法采用聚合酶链反应-限制性片断长度多态性法检测179例HBV感染者(包括118例慢性乙型肝炎和61例急性乙型肝炎)和120例健康对照人群外周血IL-6基因启动子区-597G/A和-572C/G位点基因分型。结果本研究在-597位点仅发现GG基因型,未发现GA或AA基因型,而-572位点发现CC、CG和GG基因型;对179例HBV感染者和120例健康对照人群检测发现,IL-6-572 GG基因型频率分别为15.1%和19.1%(P>0.05),而118例慢性乙型肝炎患者GG基因型(18.7%)明显高于61例急性乙型肝炎(8.2%)和健康人(11.7%),差异有统计学意义(P<0.05);在HBV感染患者G等位基因频率(47.9%)显著高于健康对照组(35.2%),但差异无统计学意义(P>0.05),而慢性乙型肝炎患者G等位基因频率(37.7%)明显高于急性乙型肝炎(22.1%)和健康对照组(26.7%),差异有统计学意义(P<0.05);多因素非条件Lo-gistic回归分析显示-572基因多态性与HBV感染后慢性化有关[P=0.038,OR=3.788(1.075～13.333)]。结论IL-6-572C/G基因多态性与HBV感染慢性化有关。     

No association of interleukin-6 gene polymorphism (-174 G/C) with premature coronary artery disease in a Turkish cohort

OBJECTIVES: Interleukin-6 (IL-6) may contribute to the inflammatory response by activating endothelial cells and stimulating the synthesis of fibrinogen. It might thus be important in the pathogenesis of inflammation associated with coronary artery disease (CAD). Several studies suggested that the -174 C allele was associated with an increased prevalence of coronary heart disease. The aim of this study was to investigate further the association of the IL-6 -174 G/C allele status with premature CAD. METHODS: A total of 120 patients and 105 controls were included in the study. The IL-6 -174 G/C polymorphism was genotyped using PCR-restriction fragment length polymorphism. RESULTS: The genotype distribution of the -174 G/C polymorphism was not different in premature CAD patients (GG: 53%; GC: 42.6%; CC: 4.3%) and controls (GG: 54.3%; GC: 39%; CC: 6.7%) (P=0.72). The prevalence of the C allele was 25.6% in patients and 26.1% in controls. By multiple regression analysis, family history, smoking, diabetes, and hypertension were independent risk factors of premature CAD, but not IL-6 genotype. CONCLUSIONS: We conclude that the IL-6 -174 G/C polymorphism is not associated with the risk of premature CAD, and does not contribute to cardiovascular risk stratification.     

老年冠心病白细胞介素-6-634C/G多态性研究

目的探讨白细胞介素-6(IL-6)基因启动子上游634C/G多态性在老年冠心病患者和正常人群中的分布及与冠心病的相关性。方法应用聚合酶链反应-限制性片断长度多态性技术对汉族104例老年冠心病患者及106例正常人白细胞介素-6基因-634C/G多态性位点进行研究,同时结合血脂、C反应蛋白、IL-6水平探讨两者之间的关系。结果-634C等位基因频率在老年冠心病患者和正常人群分别为77·9%和85·4%,G等位基因频率分别为22·1%和14·6%。冠心病患者-634GG基因型频率和G等位基因频率明显高于正常对照组(P<0·05)。结论IL-6基因-634C/G位点多态性与老年冠心病呈相关性。G等位基因可能是老年冠心病的易感性标志。     

白细胞介素-6启动子572C/G基因多态性与2型糖尿病下肢血管病变的关系

目的 从病因学角度探讨白细胞介素-6(IL-6)基因启动子-572C/G多态性与2型糖尿病并发下肢血管病变间的关系.方法 选取2008年2月至2009年1月天津医科大学总医院内分泌科住院的2型糖尿病患者280例,其中男130例,年龄(58.7±0.8)岁;女150例,年龄(58.1±0.5)岁.根据血管彩色多普勒超声检查分为下肢血管病变(VDLE)组、下肢血管神经病变(VNDLE)组、下肢神经病变(NDLE)组和无下肢并发症(NC)组.另选取2008年12月至2009年1月社区健康查体正常的人群70例作为正常对照组.取受试者静脉血提取基因组DNA,聚会酶链反应-限制性片段长度多态性(PCR-RFLP)法测定IL-6启动子区-572C/G基因多态性.各组间频率比较用X2检验,不同组间的计量资料均数比较采用单因素方差分析.结果 IL-6启动子-572C/G具有多态性分布的特点.基因型GG和CG,等位基因G频率在糖尿病组(32.1%CC,49.3%CG,18.6%GG;43.2%G,56.8%C)高于正常对照组(54.3%CC,37.1%CG,8.6%GG;27.1%G,72.9%C),差异有统计学意义(X2值分别为12.649和12.054,P<0.05);在糖尿病各组和正常对照组间差异有统计学意义(X2值分别为22.015和20.471,P<0.05);在下肢血管病变组(23.4%CC,53.9%CG,22.7%GG;49.6%G,50.4%C)高于无下肢血管病变组(36.7%CC,47.5%CG,15.8%GG;60.4%G,39.6%C),差异有统计学意义(X2值分别为6.399和5.752,P<0.05).结论 IL-6启动子-572C/G的基因型GG和CG,等位基因G可能是2型糖尿病合并下肢血管病变的易感基因,IL-6启动子-572C/G基因多态性与2型糖尿病下肢血管病变密切相关.     

Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica

OBJECTIVE: To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. METHODS: A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. RESULTS: The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 +/- 3.7 pg/ml vs 1.8 +/- 2.1 pg/ml, p = 0.01). Patients homozygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. CONCLUSION: Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.