CXCL16基因多态性与C反应蛋白的相关性研究

目的探讨健康人群趋化因子CXC配体16（CXCL16）基因多态性与血清CXCL16、C反应蛋白（CRP）水平的相关性。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测204名健康体检者CXCL16基因A181V多态性,同时分别应用酶联免疫吸附试验（ELISA）和免疫比浊法检测血清CXCL16和高敏CRP（hs-CRP）水平,并进行统计学分析。结果 AA基因型血清hs-CRP水平明显高于GG、GA基因型（P=0.01）;多元线性回归显示A等位基因是高hs-CRP水平的独立危险因素（OR=1.25,95%CI：1.08~2.59,P=0.021）;以血清hs-CRP水平中位数（0.91 mg/L）为界定值分为2组,AA基因型和A等位基因频率在hs-CRP〉0.91 mg/L组中显著升高（P=0.008,0.036）;而血清CXCL16水平与其基因型间差异无统计学意义（P〉0.05）。结论 CXCL16基因A181V位点基因多态性与血清hs-CRP水平相关,A等位基因可能参与机体炎症反应的发生、发展。     

老年高血压病患者心房颤动易感性与C-反应蛋白-717A/G多态性的关系

目的探讨C-反应蛋白（CRP）-717A/G多态性与老年高血压病患者心房颤动易感性的关系。方法选择75例合并心房颤动（房颤组）及94例无心房颤动（对照组）的老年高血压病患者,聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测CRP-717A/G基因型,比较两组基因型及等位基因频率分布,以及各基因型对血脂参数、高敏C反应蛋白（hs-CRP）的影响。结果房颤组hs-CRP水平（P=0.000 0）及左心房直径（P=0.000 0）均显著高于对照组,房颤组AA基因型频率（P=0.025 3）及A等位基因频率也显著高于对照组（P=0.028 0）。无论是房颤组抑或对照组,均未发现CRP-717A/G多态性对各临床参数有影响。结论老年高血压病合并房颤患者hs-CRP水平显著升高,CRP-717 A等位基因与房颤易感性相关。     

载脂蛋白E基因多态性与辛伐他汀调脂疗效及hs-CRP的关系

目的 研究载脂蛋白E(apoE)基因多态性与辛伐他汀调脂疗效及超敏C反应蛋白(hs-CRP)的关系.方法 采用等位基因特异性多重PCR技术,对178例高脂血症患者进行载脂蛋白E基因分型,分析基因型与血脂水平、辛伐他汀调脂疗效及hs-CRP的关系.结果 载脂蛋白E基因多态性可影响血脂水平,ε3/2组TC,LDL-C低于ε3/3组(t=2.119,P=0.046;t=3.318,P=0.003),ε4/3组TC,LDL-C高于ε3/3组(t=3.079,P=0.004;t=3.038,P=0.004);辛伐他汀治疗12周后(20 mg/d),ε3/2组血清LDL-C下降程度大于ε3/3组(t=2.124,P=0.046);辛伐他汀治疗前,携带等位基因ε4组个体hs-CRP水平低于不携带等位基因ε4组(t=2.083,P=0.043),但未发现ε4等位基因对辛伐他汀降低hs-CRP产生影响(t=0.997,P=0.324).结论 载脂蛋白E基因多态性与辛伐他汀调脂疗效相关.     

CD14 C(-260)T启动子多态性对冠心病患者C反应蛋白水平的影响

目的 探讨位于CD14基因启动子区域的C260T多态等位基因变异体CD14启动子区域-260位点C、T等位基因[CD14C(-260)T]启动子多态性对冠心病患者C反应蛋白水平的影响.方法 通过研究82例稳定性冠心病患者的高敏C反应蛋白(hs-CRP)水平检测组织炎症.结果 CD14基因中C260T多态性基因型分布如下:CC 18例(22%)、TC 48例(58.5%)、TT 16例(19.5%).相比于其它等位基因携带者TT型个体具有较高的hs-CRP(P=0.04).具有较高百分比的T等位基因纯合子其hs-CRP＞0.3mg/dl(P=0.01).结论 功能多态性的T纯合子在缺血性危险中是增高的,与hs-CRP＞0.3mg/dl是独立相关的(P=0.004).     

C反应蛋白基因＋1444C／T多态性与缺血性脑卒中的相关分析

目的探讨C反应蛋白（CRP）基因＋1444C／T多态性与缺血性脑卒中的关系。方法选择286例缺血性脑卒中患者,根据脑动脉狭窄情况分为狭窄（136例）和无狭窄（150例）两组。同期健康体检者140例为对照组,应用PCR-RFLP方法检测受试者的CRP基因型,同时测定血清高敏C反应蛋白（ks．CRP）浓度。结果狭窄、无狭窄脑卒中组血清CRP浓度均显著高于对照组（P均〈0．01）,而这两组间CRP浓度差异无统计学意义。CRP基因＋1444C／T多态性在各组人群中的分布无统计学差异（P〉0．05）。对照组CT基因型患者血清CRP浓度显著高于CC基因型患者[1．59（0．73—4．62）mg／Lvs0．67（0．10—1．81）mg／L,P〈0．01],但卒中组不同基因型个体间hs-CRP浓度无统计学差异。结论血清hs-CRP浓度与缺血性脑卒中相关,而与卒中患者狭窄与否无关。CRP基因＋1444C／T多态性与缺血性脑卒中无相关性,但其与健康人群血清CRP浓度有关。     

痛风性关节炎患者血清 IL-1β，TNF-ɑ，hs-CRP水平及与 IL-1β基因启动子区 rs2853550 A/G位点多态性相关性分析

目的　分析深圳地区痛风性关节炎（ gouty arthritis,GA）患者血清白细胞介素 -1β（interleukin-1β,IL-1β）、肿瘤坏死因子（ tumor necrosis factor,TNF-ɑ）、超敏 -C反应蛋白（ hypersensitive C-reactive protein,hs-CRP）水平及与 IL-1β基因启动子区 rs2853550 A/G位点多态性相关性。方法　收集 GA确诊患者 216例作为 GA组,同时选取 153例健康体检人群作为对照组。分别检测血清 IL-1β,TNF-ɑ及 hs-CRP水平,同时检测 IL-1β基因 rs2853550 A/G多态性。结果　GA组 IL-1β,TNF-ɑ及 hs-CRP水平分别为 5.16±1.02pg/ml,21.84±6.49pg/ml和 17.03±5.61mg/L,明显高于对照组（ 3.94±0.87pg/ml,3.50±1.16pg/ml及 2.14±0.73mg/L）,差异均有统计学意义（ t=4.217 3,20.510 4,23.274 5,均 P<0.05）。GA组 IL-1β基因 rs2853550 A/G位点 GG基因型和 G等位基因频率（ 75.93%和 83.56%）明显高于对照组（ 51.63%和 60.13%）,差异有统计学意义（ χ2=5.641 9,5.037 2,均 P<0.05）。GG基因型和 G等位基因患 GA的相对风险明显增加（ OR=7.092,95%CI:5.681~10.526和 OR=5.914,95％ CI:3.514～ 8.029）,而 AA基因型和 A等位基因患 GA的相对风险明显降低（ OR=0.731,95%CI:0.576～ 0.918和 OR=0.584,95％ CI:0.437~0.753）。GA组 GG基因型 IL-1β水平（5.42±1.12pg/ml）明显高于 GA基因型（ 4.51±0.67pg/ml）,而 GA基因型明显高于 AA基因型（ 4.04±0.29pg/ml）,不同基因型之间差异有统计学意义（ F=8.019 5,P=0.023 6）。经 Spearman相关性分析, GA组 IL-1β与 TNF-ɑ,hs-CRP水平呈正相关（ r=0.790 1,0.684 7,均 P<0.05）。结论　GA患者 IL-1β,TNF-ɑ及 hs-CRP水平明显升高,且存在一定相关性。同时 IL-1β基因启动子区 rs2853550 A/G位点呈多态性,其中 GG基因型可能与 GA发病具有一定的相关性。     

白细胞介素-18基因-607C/A多态性与2型糖尿病的相关性

目的研究白细胞介素-18（interleukin 18,IL-18）基因单核苷酸多态性与河北唐山地区人群2型糖尿病（T2DM）的相关性。方法应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对122名T2DM患者和161名健康对照者（NC）行IL-18启动子-607C/A基因型检测,并测定血清hs-CRP。结果糖尿病与对照组比较,IL-18基因-607C/A多态性分布差异有统计学意义（P〈0.05）,C等位基因携带者患T2DM的风险是A等位基因的1.883倍（OR=1.883,95%CI：1.28-2.771）。两组人群中CC和CA基因型个体CRP浓度均显著高于AA基因型个体（P〈0.05）。结论IL-18基因-607C/A多态性与T2DM的发病具有相关性,其中C等位基因可能是T2DM的遗传易感基因,并导致血清CRP浓度升高。     

CD14C（-260）T启动子多态性对冠心病患者C反应蛋白水平的影响

目的探讨位于CD14基因启动子区域的C260T多态等位基因变异体CD14启动子区域-260位点C、T等位基因[CD14C(-260)T]启动子多态性对冠心病患者C反应蛋白水平的影响。方法通过研究82例稳定性冠心病患者的高敏C反应蛋白(hs-CRP)水平检测组织炎症。结果CD14基因中C260T多态性基因型分布如下:CC18例(22%)、TC48例(58.5%)、TT16例(19.5%)。相比于其它等位基因携带者TT型个体具有较高的hs-CRP(P=0.04)。具有较高百分比的T等位基因纯合子其hs-CRP>0.3mg/dl(P=0.01)。结论功能多态性的T纯合子在缺血性危险中是增高的,与hs-CRP>0.3mg/dl是独立相关的(P=0.004)。     

中国汉族人群CRP＋1444C／T基因多态性与颅内动脉粥样硬化程度的关系

目的 研究中国汉族人群C反应蛋白(CRP)+1444C/T基因多态性与颅内动脉粥样硬化程度的关联.方法 应用PCR-RFLP方法检测来自北京天坛医院的246例单独颅内动脉狭窄患者CRP +1444C/T基因多态性,同时测定血清hs-CRP浓度.根据颅内狭窄血管数的第50百分位数把病人分为两组:较低和较高程度组.结果 较高与较低程度组比较,血清hs-CRP浓度差异无统计学意义,而CRP+1444C/T基因型和等位基因频率分布差异有统计学意义(CC vs. CT+TT).与T等位基因携带者比较,CC基因型个体发生较高程度动脉粥样硬化的风险增加(OR:4.040;95%CI:1.150～14.195;P=0.029).结论 CRP+1444 C/T基因多态性与颅内脑动脉粥样硬化程度有关,而血清CRP浓度与之无关.     

血清CXC趋化因子配体16水平与急性脑梗死患者颈动脉粥样硬化斑块关系研究

目的探讨急性脑梗死(ACI)患者血清CXC趋化因子配体16(CXCL16)水平与颈动脉粥样硬化的相关性。方法选取36例ACI患者为ACI组,同期体检者30例为对照组,检测血脂、超敏C反应蛋白(hs-CRP)和血清CXCL16水平,并应用彩色多普勒超声检查颈动脉粥样硬化斑块及颈动脉内膜-中膜厚度(IMT)变化情况。结果ACI组血清CXCL16水平[3.58(1.06~12.83)ng/L]高于对照组[1.57(0.61~3.34)ng/L],差异有统计学意义(P0.05);ACI组颈动脉IMT[(1.19±0.36)mm]高于对照组[(1.01±0.18)mm],差异有统计学意义(P0.05);ACI组中,不稳定性斑块患者CXCL16水平高于稳定性斑块患者,差异有统计学意义(P0.05),血清CXCL16水平与颈动脉IMT和hs-CRP水平均呈正相关(r=0.497,P0.05;r=0.442,P0.05);多元线性逐步回归分析显示,CXCL16是动脉粥样硬化斑块形成的重要危险因子之一。结论高血清CXCL16和hs-CRP水平为颈动脉粥样硬化斑块形成的独立危险因素,CXCL16与颈动脉粥样硬化斑块的易损性密切相关。     

Soluble C-X-C chemokine ligand 16 levels are increased in gout patients

ObjectivesSoluble C-X-C chemokine ligand 16 (CXCL16) was shown to recruit polymorphonuclear cells into synovial tissue in gout patients. The aim of this study was to explore the pathophysiological characteristics of CXCL16 in gout patients with or without chronic kidney disease (CKD).Design and methods42 gout patients, 22 CKD and 20 healthy subjects were enrolled. Plasma CXCL16 and other biochemical parameters were tested.ResultsPlasma CXCL16 levels in gout subjects with CKD were significantly increased compared with healthy, CKD and gout subjects without CKD. Soluble CXCL16 levels in gout subjects were closely correlated with renal function and lipid profiles, and independently associated with 24 h proteinuria, creatinine clearance rate and C-reactive protein.ConclusionOur data indicated that plasma CXCL16 levels are significantly increased in gout patients with and without CKD, and are independently associated with renal function. Elucidating the pathophysiologcial role of CXCL16 in gout patients requires further study.     

高胆固醇血症患者LDL-R基因XspI位点多态性与血清IL6的关系及意义

摘要：目的：探讨高胆固醇血症患者低密度脂蛋白受体基因（LDL-R）第2外显子Xsp-I位点多态性与血清IL-6的关系及意义。 方法：用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术结合DNA测序检测730例高胆固醇血症患者和200例体检健康者LDL-R基因的Xsp-I酶切位点多态性;按基因型分组,用ELISA法检测各基因型IL-6的浓度,对两者关系进行分析。用多元逐步回归分析影响IL-6水平的因素。 结果：与健康对照组相比,高胆固醇血症组血清IL-6明显升高,HDL-C降低（P均<0.05）;基因型分别为X^-X^-、X⁺X^-、X⁺X⁺基因型的高胆固醇血症患者,TC、LDL-C、IL-6水平依次升高,HDL-C水平依次降低,差异有统计学意义（P均<0.05）;多元线性回归分析显示基因型和胆固醇水平是影响IL-6水平的独立因素。 结论：高胆固醇血症患者血清IL-6水平升高,LDL-R基因X⁺X⁺基因型可能通过影响IL-6水平促进高胆固醇血症。     

急性胰腺炎患者血清TNF-a和CRP水平的测定及其临床意义

目的探讨TNF-a、CRP变化在急性胰腺炎的临床意义。方法测定轻症急性胰腺炎和重型急性胰腺炎患者入院第1、4、7、14天时血清TNF-a和CRP水平，并与健康人对照。结果入院时和入院后重症急性胰腺炎血清TNF-a和CRP水平均高于轻症急性胰腺炎，而后者又均高于健康组（P＜0．05），且血清TNF-a含量和CRP含量变化呈正相关（r=0.7124,P＜0．05）。结论血清TNF-a和CRP水平变化与AP病情变化密切相关，联合检测有助于了解病情发展。     

血清C反应蛋白水平与脑梗死预后的关系

目的探讨血清c反应蛋白（CRP）水平与脑梗死患者预后的关系。方法对114例脑梗死患者（脑梗死组）及健康体检者80例（对照组）均采用散射浊度法测定血清CRP水平,参照临床神经功能缺损程度评分标准（NDS）评估脑梗死患者的预后,对血清CRP水平与脑梗死患者预后的关系进行分析。结果脑梗死组血清CRP阳性78例,阳性率为68．42％,对照组血清CRP均阴性。脑梗死组血清CRP水平为（6．51±1．95）mg·-1,对照组血清CRP水平为（1．62±0．87）mg·L-1,脑梗死组血清CRP水平明显高于对照组（P〈0．01）。脑梗死组患者血清CRP水平随NDS评分的下降而增高,脑梗死组各亚组间血清CRP水平比较差异有统计学意义（P〈0．05）。结论血清CRP水平与脑梗死预后关系密切,血清CRP水平越高,病情越重,预后越差;而血清CRP水平越低则其预后越好。CRP可作为监测及评估脑梗死患者预后情况的重要指标：降低血清CRP水平有助于减低脑梗死发生率及改善脑梗死患者的预后。     

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 effects of haemodialysis and peritoneal dialysis on serum lipoprotein(a) and C-reactive protein levels

Elevated serum lipoprotein(a) is an independent risk factor for coronary artery disease, and C-reactive protein (CRP) is a general and cardiovascular marker in haemodialysis patients. We studied lipoprotein(a) and CRP levels in 48 haemodialysis and 24 continuous ambulatory peritoneal dialysis (CAPD) patients and 20 healthy individuals, after a 12 h fast. Serum lipoprotein(a) levels were elevated in 31.3%, 66.7% and 5% of haemodialysis and CAPD patients and control subjects, respectively. The difference between all groups was significant. Serum CRP levels were high in 43.8%, 58.4% and 5% of haemodialysis and CAPD patients, and healthy subjects, respectively. The mean serum CRP level was significantly different between all groups. Both protein levels were higher in CAPD patients than haemodialysis patients, suggesting that CAPD patients should be more closely monitored for coronary artery disease.     

C-reactive protein gene polymorphism 1009A>G is associated with serum CRP levels in Chinese men: a TCVGHAGE study

BACKGROUND: Increased concentrations of high-sensitivity CRP (hs-CRP) are associated with increased risk of cardiovascular disease. This increase might be caused by low-grade inflammation, but a number of studies have suggested that serum CRP concentrations are under genetic control. Since the relation between CRP concentration and cardiovascular diseases occurs across ethnicities, we determined whether CRP gene variants affect fasting hs-CRP concentrations in a cohort of Chinese men. METHODS: High-sensitivity CRP concentrations were measured in 369 Chinese men. Six polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing within the CRP gene: 969T>C, 1009A>G, and a 3-allele polymorphism 1440C>A>T in the 5' UTR (promoter region), 2667G>C in exon 2, and 3872A>G and 5992T>A in the 3' UTR. RESULTS: In a group of participants (n=328) whose fasting serum hs-CRP concentrations were within the 5th to 95th percentile, we found that the genetic polymorphism 1009A>G was significantly associated with fasting serum hs-CRP concentrations (GG vs. AG or AA genotypes, CRP concentrations 0.072+/-0.062 vs. 0.176+/-0.166 and 0.166+/-0.185 mg/dl, mean+/-S.D., both P=0.023). Furthermore, subjects carrying the 1009G bearing haplotype exhibited the lowest CRP concentrations (P=0.05). CONCLUSION: The CRP 1009A>G genotypes and associated haplotypes were associated with lower fasting serum hs-CRP concentrations in a group of elderly Chinese men.     

肝脂酶启动子250 G/A多态性与血脂的关系

目的探讨各项血脂水平与肝脂酶(HL)启动子250 G/A基因多态性的关系。方法运用聚合酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP),对112例三酰甘油(TG)正常者和103例高TG者的HL启动子250 G/A基因多态性进行研究。结果发现HL启动子250 AA等位基因频率在高TG组为0.447 7明显高于正常TG组(0.263 4,P<0.05)。在总研究组发现AA型的TG、载脂蛋白B(ApoB)浓度明显高于GG型和GA型,而载脂蛋白A l(ApoA l)则明显降低(P<0.05)。按性别分层后发现AA型女性和男性的TG、低密度脂蛋白胆固醇(LDL-C)的浓度明显高于非AA型同性(P<0.05),而高密度脂蛋白胆固醇(HDL-C)、ApoA l浓度分别低于非AA型的同性(P<0.05)。经Logistic回归分析显示年龄、LDL-C、ApoB、AA型是危险因子,而HDL-C是保护因子。结论HL启动子250 G/A多态性与高TG血症的发生相关,并可影响血浆脂类的代谢,可能是高TG所致疾病的危险因素。