白介素6基因启动子区多态性与体重指数和炎症因子等生化指标的相关性及与冠心病发生发展关系的探索

本研究旨在通过对中国北方地区汉族人IL-6基因启动子区-572G／C，-597G／A多态性与体重指数（BMI）和炎症因子等生化指标的相关性的调查，探索基因多态性与冠心病（CHD）发生发展的关系。采用荧光杂交探针、以荧光共振能量转移原理和熔点曲线分析技术，测定了194例冠心病患者和123例健康对照者的IL-6基因型，同时测定BMI、超敏C反应蛋白（hsCRP）、血脂、载脂蛋白等指标，并通过建立逻辑回归（Logistic regression）模型分析CHD发生的危险因素。结果表明，在所有观察对象中发现中国北方汉族人IL-6基因启动子区-597位点有7例为GA型．其余均为GG型，尚未发现AA型，未发现其多态性与BMI和炎症因子等生化指标的相关性。冠心病（cor—onary heart disease，CHD）组与对照组-572G／C基因型频率和等位基因频率分布差异无统计学意义，但是CHD组和对照组携带G等位基因和非G等位基因频率相比差异有统计学意义（P=0，0425）。正常对照组中携带G等位基因者收缩压中位数水平明显高于非G等位基因者（P=0、02）。在所有研究对象中，与非G等位基因组相比，携带G等位基因组的体重指数、超敏C反应蛋白、收缩压中位数水平显著升高（P值分别为0、026、0．022、0、005）。经Logistic逐步回归分析显示，年龄、血清甘油三脂、性别、高血压、载脂蛋白C2、血清总胆固醇、脂蛋白a是冠心病发生的危险因子，而载脂蛋白A1是保护因子（P〈0．05），未见-572G／C的G等位基因是一独立的危险因素。结论：IL-6基因启动子区-597G／A多态性和CHD的易感性无关，而-572G／C多态性与CHD的易感性有关，其机制可能与-572G／C多态性可导致BMI、hsCRP和血压的变化有关。     

IL-6基因启动子区域-572C>G和-174G>C多态性与江苏宿迁汉族人群冠心病的相关性

目的 探讨白细胞介素6(interleukin-6,IL-6)基因启动子区域-572C>G和-174G>C基因多态性与宿迁汉族人群冠心病(coronary heart disease,CHD)的关系。方法 参考2010卫生部CHD诊断标准(WS319-2010),选择2017年1～12月在宿迁市第一人民医院心内科确诊的CHD患者,应用聚合酶链-限制性片段长度多态性(Polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)方法检测266例CHD患者和192例体检健康人群(对照组),分析其IL-6-572C>G和IL-6-174G>C基因多态性,并进行Hardy-Weinberg平衡检验,检测血糖、血脂等生化指标。结果 IL-6-572C>G基因型和等位基因频率在两组间分布差异有统计学意义(χ2=11.1,19.5,22.4,均P<0.05),CHD组GG型和CG型OR值分别是CC型的4.88倍(95%CI:2.31～10.31)和1.96倍(95% CI:1.32～2.91); -174G>C基因型和等位基因频率在两组间分布差异无统计学意义(χ2=0.024,0.027,均P>0.05)。结论 IL-6-572G等位基因可能是宿迁汉族CHD的易感基因,IL-6-174G>C基因多态性可能与宿迁汉族人群CHD没有相关性。     

白细胞介素6基因-174G/C和-634C/G多态性与冠心病的相关性研究

目的探讨白细胞介素6(interleukin6,IL6)基因启动子上游174G/C和634C/G基因多态性,在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199例冠心病患者及189名正常人群,白细胞介素6基因174G/C、634C/G位点进行研究,同时结合血脂、脂蛋白和载脂蛋白水平,探讨两者之间的关系。结果正常人群和冠心病患者的174G等位基因频率均为0.99。174C等位基因频率均为0.01。634C等位基因频率在正常人群和冠心病患者分别为0.82和0.76,G等位基因频率分别为0.18和0.24,两者差异有统计学意义(P<0.05)。冠心病患者634GG基因型频率(0.08)明显高于对照组(0.02)(P<0.05)。结论白细胞介素6基因174位点多态性与冠心病无关,而634位点多态性与冠心病有相关性。G等位基因可能是汉族人群冠心病的易感性标志。     

白细胞介素-6基因-572G/C多态性对急性冠状动脉综合征患者血浆高敏C反应蛋白的影响

目的研究白细胞介素-6（IL-6）基因-572G／C多态性对急性冠状动脉综合征患者血浆高敏C反应蛋白（hs-CRP）浓度的影响。方法采用聚合酶链反应结合限制性内切酶片段长度多态分析方法（PCR-RFLP）检测228例急性冠状动脉综合征患者的IL-6基因-572G／C多态性，用免疫比浊法测定hs-CRP浓度。结果①ST段抬高急性心肌梗死（STEMI）组hs—CRP水平明显高于非ST段抬高急性冠脉综合征（NSTEACS）组，差异有统计学意义（P〈0．05）。②IL-6基因-572G／C多态性的基因型频率：CC42．54％、GC46．92％、GG10．52％；等住基因频率：C66．01％、T33．99％。③在STEMI组中，基因型CC组hs-CRP浓度较基因型GG＋GC组高，差异有统计学意义（P〈0．05）。多因素线性回归分析结果仍显示基因型CC携带者的血浆hs-CRP水平较携带G等住基因者高（P〈0．05）。在NSTEACS组及总人群中，不同基因型组hs—CRP比较差异无统计学意义（P〉0．05）。结论IL-6基因-572G／C多态性对急性冠状动脉综合征患者血浆hs-CRP水平无影响。在STEMI患者中，基因型CC携带者的血浆hs-CRP水平较携带G等住基因者高，提示IL-6基因-572G／C多态性在较高的炎症反应状态下，会对hs-CRP的表达产生影响。     

IL-6基因-572C／G多态性对2型糖尿病患者血清IL-6水平的影响

【目的】探讨白介素-6（IL-6）基因-572C／G多态性对2型糖尿病患者血清IL-6水平的影响。【方法】应用聚合酶链反应-限制性片段长度多态性方法检测358例初发2型糖尿病患者IL-6基因-572C／G多态性,用ELISA方法检测不同基因型患者的IL-6水平【结果】2型糖尿病患者IL-6基因-572CC,CG,GG基因型人数分别为212,129,17;血清IL-6水平分别为（61．32±16．98）pg／mL,（64．98±15．19）pg／mL和（92．18±25．36）pg／mL,血清IL-6水平在CC,CG基因型间差异无显著性,两种基因型与GG基因型相比,血清IL-6水平差异均有显著性（P〈0．05）。【结论]IL-6基因572C／G多态性可能具有功能性,572GG基因型分泌IL-6能力可能较CC及CG基因型强,IL-6基因572GG基因型可能是2型糖尿病的危险因素之一。     

白细胞介素-6基因多态性与冠心病的相关性研究及其对血脂的影响

目的 探讨白细胞介素6（IL-6） 基因启动子区基因-572位点和-634位点多态性与冠心病的关系,及其对血脂、脂蛋白、载脂蛋白水平的影响.方法 采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法,检测165例冠心病（冠心病组）患者和170名健康人（对照组） 的IL-6基因型;按常规方法测定血脂、脂蛋白、载脂蛋白水平.结果 冠心病组总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）水平均明显高于对照组（P均〈0.05）;IL-6基因-634位点多态性在冠心病组和对照组的分布差异无显著性（P〉0.05）,而IL-6基因-572位点多态性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,G等位基因携带者患冠心病的风险是C等位基因的1.652倍[相对比值比（OR）=1.652,95%可信区间（CI）：1.137～2.401],携带G等位基因的冠心病个体血清TC水平显著高于不携带者（P〈0.05）.结论 IL-6基因-572位点多态性与冠心病的发病具有相关性,其中G等位基因是冠心病重要的遗传标记;IL-6基因-572位点多态性可能通过影响血脂水平而影响冠心病的发生.     

单采献血者IL-28b基因多态性与隐匿性HBV感染相关性研究

目的　研究单采献血者白细胞介素-28b（IL-28b）基因多态性与隐匿性乙型肝炎病毒（HBV）感染（OBI）相关性。方法　选择2016年1月～2019年12月山东省血液中心成功捐献血小板HbsAg（-）、核酸检测（NAT）无反应的献血者1 158例为研究对象,提取献血者血液DNA,采用直接测序法进行IL-28b基因分型,cobas HBV定量核酸检测试剂盒检测血液HBV-DNA载量,Logistic回归分析IL-28b基因rs8099917位点、rs12979860位点多态性与OBI的关系。结果　与非OBI比较,OBI献血者IL-28b基因rs8099917位点G等位基因频率、TG+GG基因型频率显著降低,T等位基因频率、TT基因型频率显著增加（χ2=22.137,22.163,均P<0.01）;rs12979860位点T等位基因频率、CT+TT基因型频率显著降低,C等位基因频率、CC基因型频率显著增加（χ2=16.378,19.091,均P<0.01）。OBI献血者rs8099917位点,与TT基因型比较,TG+GG基因型患者HBV-DNA载量显著降低（t=5.257,P<0.01）;rs12979860位点,与CC基因型比较,CT+TT基因患者HBV-DNA载量显著降低（t=17.398,P<0.01）,以上比较差异均有统计学意义。Logistic回归分析结果显示,rs8099917位点,与TT基因型比较,TG+GG基因型可显著降低OBI发生风险（95% CI:0.288~0.843,P<0.05） ;rs12979860位点,与CC基因型比较,CT+TT基因型可显著降低OBI发生风险（95% CI :0.207~0.761,P<0.05）。结论　单采献血者OBI可能与IL-28b基因rs8099917位点、rs12979860位点多态性有关。     

炎症细胞因子基因多态性与癌因性疲乏的关联研究

目的 探讨炎症细胞因子基因多态性与癌因性疲乏(CRF)的关联,为研究遗传易感性在CRF发生发展中所起的作用提供研究基础。方法 肺癌患者242例,其中癌因性疲乏组162例,非癌因性疲乏组80例。通过PCR RFLP进行基因分型,分析基因型及等位基因频率在疲乏组与非疲乏组的分布情况及炎症细胞因子基因多态性与癌因性疲乏的关联性。结果 TNFα 308G/A、IL 1β 511C/T基因型分布在两组间差异有统计学意义(P均<0.05)。多元logistic回归校正了年龄和性别等混杂因素后显示,相对于TNFα 308GG基因型患者,携带GA/AA基因型患者发生CRF的风险降低了74%（15%~92%）;相对于IL 6 174GG基因型患者,携带GC/CC基因型患者发生CRF的风险降低了78%（0%~95%）;在IL 1β 511C/T基因位点中,携带CC基因型的患者发生CRF的风险是TT基因型患者的3.96倍（95%CI 1.02 15.45）。结论 携带TNFα 308GG、IL 6 174GG、IL 1β 511CC基因型的肺癌患者发生癌因性疲乏的风险明显增加。     

白细胞介素6基因启动子区两个突变位点多态性检测方法的建立

目的建立一种快速检测IL-6基因启动子区-597G／A、-572G／C多态性的双重实时荧光PCR方法。方法采用1对引物，2对荧光标记探针，结合荧光共振能量转移原理和熔点曲线分析技术，检测IL-6基因启动子区-572G／C，-597G／A2个位点多态性。结果用建立的双重实时荧光PCR方法对123名健康查体者进行检测，发现中国汉族人IL-6基因启动子区-572位点有3种基因型，分别为GG，GC，CC型；-597位点仅发现4名为GA型，其余均为GG型，尚未发现从型。结论双重实时荧光PCR法简便快速，与其他方法比较具有准确、经济的特点，适合临床基因快速分型。     

Gender and ethnic differences in a case-control study of dyslipidemia: using the apolipoprotein A-V gene as an exemplar in cardiovascular genetics

Common, complex genetic disorders such as coronary heart disease (CHD) frequently show large population differences, contributing to health disparities. It is also well known that CHD risk factor profiles and the frequency of coronary events differ by gender. Study of premature CHD has revealed that apolipoproteins are important discriminating factors for distinguishing individuals with CHD. Recent findings indicated that apolipoprotein A-V (APOA-V) gene promoter polymorphisms are an important determinant of plasma triglycerides (TG) and lipoprotein cholesterol, and a risk factor for CHD. Variations in APOA-V may have varying impacts in different ethnic groups. The purpose of this interdisciplinary genetic research project was to determine (1) the association of the APOA-V polymorphisms with lipoprotein profiles, and (2) the gender and ethnic differences in the T-1131C promoter polymorphism of the APOA-V gene in individuals with dyslipidemia versus controls. Results indicate that the minor -1131C allele (CC homozygotes + CT heterozygotes) was associated with elevated plasma TG (p = 0.007), very low density lipoprotein (VLDL)-TG (p = 0.019), LDL-TG (p = 0.004), high-density-lipoprotein (HDL)-TG (p < 0.001), and VLDL-cholesterol (p = 0.008). We found a striking elevation in the frequency of the minor C allele in Asians (p < 0.001) compared to Europeans. We also found a significant difference in genotype frequency between men and women in Asians (p = 0.031) and Europeans (p < 0.01). Remarkably, Asian women with the C allele have a 36% increase in TG compared to Asian women homozygous for the T allele. In summary, we found significant ethnic-specific and gender-based differences in the frequency of the minor allele of the -1131 APOA-V gene promoter polymorphism. Identification of genetic variations among ethnic groups and between genders may have significant potential for a better understanding of the development of cardiovascular disease.     

The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels,and an association with systemic-onset juvenile chronic arthritis.

During active disease, patients with systemic-onset juvenile chronic arthritis (S-JCA) demonstrate a rise and fall in serum interleukin-6 (IL-6) that parallels the classic quotidian fever. To investigate the possibility that this cytokine profile results from a difference in the control of IL-6 expression, we examined the 5'' flanking region of the IL-6 gene for polymorphisms. A G/C polymorphism was detected at position -174. In a group of 383 healthy men and women from a general practice in North London, the frequency of the C allele was 0.403 (95% confidence interval 0.37-0.44). In comparison, 92 patients with S-JCA had a different overall genotype frequency, especially those with onset of disease at < 5 yr of age. This was mainly due to the statistically significant lower frequency of the CC genotype in this subgroup. When comparing constructs of the 5'' flanking region (-550-+61 bp) in a luciferase reporter vector transiently transfected into HeLa cells, the -174C construct showed 0.624+/-0.15-fold lower expression than the -174G construct. After stimulation with LPS or IL-1, expression from the -174C construct did not significantly change after 24 h, whereas expression from the -174G construct increased by 2.35+/-0.10- and 3.60+/-0.26-fold, respectively, compared with the unstimulated level. Plasma levels of IL-6 were also measured in 102 of the healthy subjects, and the C allele was found to be associated with significantly lower levels of plasma IL-6. These results suggest that there is a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. The reduced frequency of the potentially protective CC genotype in young S-JCA patients may contribute to its pathogenesis. Similarly the individual''s IL-6 genotype may be highly relevant in other conditions where IL-6 has been implicated, such as atherosclerosis.     

三酰甘油/高密度脂蛋白胆固醇比值对青少年肥胖人群非酒精性脂肪性肝病的预测价值

目的:探讨三酰甘油/高密度脂蛋白胆固醇比值(TG/HDL-C)对肥胖青少年非酒精性脂肪性肝病(NAFLD)的预测价值。方法:选取2012年8月至2017年8月无锡市第二人民医院内分泌科门诊或住院的肥胖青少年患者共114例,收集腰围(WC)、体质指数(BMI)、血压(BP)、氢质子磁共振波普数据(~1H-MRS)、血清谷丙转氨酶(ALT)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)及胰岛素(INS)等临床指标,计算TG/HDL-C及稳态模型胰岛素抵抗指数(HOMA-IR)。结果:两组患者的年龄、性别、BMI、TC、腰围、舒张压、ALT和空腹血糖及胰岛素差异无统计学意义。高TG/HDL-C组患者收缩压和肝脏三酰甘油含量均显著高于低TG/HDL-C组(P0.05)。多因素Logistic回归分析提示:TG/HDL-C是青少年肥胖人群患NAFLD的独立危险因素(OR=5.78,95%CI 2.23～14.97)。TG/HDL-C预测青少年肥胖人群患NAFLD的ROC曲线下面积为0.73,以2.64为诊断界点时,灵敏度为72.5%,特异度为71.6%。结论:TG/HDL-C有助于预测肥胖青少年人群NAFLD的患病风险。     

青岛地区哮喘患者IL-6基因启动子-634C/G位点多态性研究

目的:了解白细胞介素-6(interleukin-6,IL-6)基因启动子区域单核苷酸多态位点-634C/G与青岛地区汉族人群过敏性哮喘的相关性.方法:采用聚合酶链反应-限制性片段长度多态性分析方法对青岛地区479例健康个体和481例过敏性哮喘患者IL-6基因启动子-634C/G多态性进行观察.结果:过敏性哮喘组与健康对照组CC、CG和GG基因型以及C和G等位基因频率分布均无统计学差异,携带GG、CG、CC基因型个体哮喘患病风险依次递增.结论:IL-6基因启动子-634C/G位点多态性与青岛地区人群过敏性哮喘发生无相关性,但携带CC等位基因型的个体过敏性哮喘的发病风险可能增加.     

肥胖儿童高尿酸血症与胰岛素抵抗、血脂的相关分析

目的探讨肥胖儿童血清尿酸(UA)与胰岛素抵抗、血脂的相关性。方法选取本院655例肥胖儿童设为观察组,另选取同时期655例健康非肥胖儿童作为对照组,分别检测两组儿童血清UA、空腹血糖(FPG)、空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C),并计算胰岛素抵抗指数(HOMA-IR)。再按照血清UA水平将观察组分为高UA血症组(HUA组)和正常UA血症组(NUA组)。结果观察组血清UA、FPG、FINS、TC、TG、LDL-C,HOMA-IR显著高于对照组,血清HDL-C显著低于对照组,差异有统计学意义(P0.05)。HUA组血清FPG、FINS、TG,HOMA-IR显著高于NUA组,差异有统计学意义(P0.05),HUA组与NUA组血清TC、HDL-C、LDL-C相比差异无统计学意义(P0.05)。经Pearson直线相关分析,肥胖儿童血清UA与FINS、TC、TG、LDL-C,HOMA-IR呈显著正相关,而与血清HDL-C呈显著负相关(P0.05)。结论肥胖儿童高UA血症与胰岛素抵抗、血脂代谢紊乱密切相关。     

PGC-1α基因多态性与冠心病的相关性分析

目的研究过氧化物酶体增殖物激活受体7共激活因子1α（PGC-1α）基因的单核苷酸多态性（single-nucleotidepolymorphism,SNP）住点rs2970847与中国汉族人群冠心痛（coronaryheartdisease,CHD）的相关性。方法本研究共选取中国汉族冠心病患者231人（男性151,女性80）,正常对照组478人（男性297,女性181）。采用限制性酶切片段长度多态性（Restriction Fragment Length Polymorphism,RFLP）的方法对rs2970847进行基因分型。并测定所有入选对象的体重指数、血糖、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白等指标。结果冠心病患者中,rs2970847位点的CC基因型为144人（62．3％）,CT基因型为75人（32．5％）,TT基因型为12人（5．2％）;而正常对照中,CC基因型为235A-（49．2％）,CT基因型为201人（42．1％）,TT基因型为42人（8．8％）。rs2970847位点与冠心痛显著相关（P=0．0009）,纯合子CC基因型可以增加冠心病的患病风险（ORCC：2．14,95％CI=1．09-4．21）。结论PGC—1α基因多态位点rs2970847与冠心痛具有显著相关性,其CC基因型是冠心病的危险因素。     

Additive effect of interleukin-6 and C-reactive protein (CRP) single nucleotide polymorphism on serum CRP concentration and other cardiovascular risk factors

BACKGROUND: Serum C-reactive protein (CRP) levels, closely associated with cardiovascular disease (CVD) risk are influenced by CRP or interleukin-6 (IL-6) single nucleotide polymorphism (SNPs). However, it is still controversial. Therefore, we investigated the association of IL-6/CRP SNPs and serum CRP levels or other CVD risk factors in healthy adult Korean men. METHODS: In healthy adult men (age>or=20 years, n=677), we genotyped IL-6-572C>G and CRP SNPs (-717G>A, 1444C>T, 2147A>G) and measured anthropometric parameters, lipid profile, serum levels of CRP and IL-6 and insulin resistance. RESULTS: At IL-6-572C>G (n=677), subjects with G/G genotype (n=42) showed higher concentrations of CRP (P=0.027) and IL-6 (P=0.028) as compared with C allele carriers after age-adjustment (C/C: n=371, C/G: n=264). Fasting insulin and homeostatis model assessment insulin resistance (HOMA-IR) were also higher in G/G genotype. However, there were no significant differences in other metabolic biomarkers. Among 677 study subjects, 676 were genotyped at CRP-717G>A (G/G: n=513, G/A: n=150, A/A: n=13), 672 at CRP+1444C>T (C/C: n=580, C/T: n=85, T/T: n=7), and 668 at CRP+2147A>G (A/A: n=273, A/G: n=296, G/G: n=99). There were no significant differences in CRP concentrations and other markers related to CVD risk according to each CRP SNP genotype. However, we could find the additive gene-gene interaction between IL-6-572C>G and CRP SNPs on CRP concentration; subjects with the 'G/G' at IL-6-572 showed the highest CRP levels when they have variant allele at CRP SNPs after adjusted for age, body mass index, cigarette smoking and alcohol drinking (-717G>A: F=7.806, P=0.005; CRP+1444C>T: F=8.398, P=0.004; and CRP+2147A>G: F=7.564, P=0.006, respectively) Particularly, G allele carriers at CRP+2147A>G in subjects with IL-6-572G/G showed highest HOMA-IR (F=9.092, P=0.003). CONCLUSION: The present data showed that serum CRP levels and other CVD risk factors appeared more influenced by IL-6-572C>G rather than CRP SNPs (-717G>A, 1444C>T, and 2147A>G), however CRP levels and insulin resistance may be additively affected by IL-6-572 and CRP SNP, particularly when subjects with G/G genotype at IL-6-572 have allele variant at CRP SNPs.     

The effect of the Interleukin-6-174G > C promoter gene polymorphism on endothelial function in healthy volunteers

AIMS: Atherosclerosis is a chronic inflammatory condition, manifest in its early stages by endothelial dysfunction. Interleukin-6 (IL6) plays a key role in driving this process through stimulation of acute phase protein synthesis. We have examined the effect of the IL6 gene -174G > C promoter polymorphism on endothelial function in a group of healthy subjects. METHODS: 248 adults aged 20-28 years participated. Polymerase chain reaction was performed for the -174G > C polymorphism. Brachial artery diameter was measured at rest and after forearm cuff occlusion by high-resolution ultrasound. Responses were represented as absolute flow mediated dilatation (FMDA). RESULTS: Overall there was a trend towards greater FMDA for genotype CC, P = 0.14. No effect was seen in women; however, in men, following multivariate analysis, there was a significant association between genotype and FMDA, P = 0.04. In addition, a significant detrimental effect of smoking on FMDA was only seen in males of genotype CC (P < 0.05) when compared to nonsmokers of the same genotype. CONCLUSION: IL6-174G > C promoter polymorphism influences endothelial function in healthy male subjects. The detrimental effect of smoking on endothelial function is most clearly seen in men of genotype -174 CC, suggesting a genotype-specific interaction with smoking.