Effect of obesity on the association between ATF3 gene haplotypes and C-reactive protein level in Taiwanese

ObjectiveATF3 has traditionally been related to various inflammatory processes. Our aim was to test the statistical association between variations in the ATF3 gene and levels of nine serum inflammatory markers, including C reactive protein (CRP), in a Taiwanese population using interaction analysis.MethodsA sample population of 604 Taiwanese subjects was enrolled. Five tagging single nucleotide polymorphisms of the ATF3 gene from the Han Chinese HapMap Database were selected and genotyped.ResultsWith or without adjustment for clinical covariates, ATF3 genotypes were found to be associated with CRP levels but not with other inflammatory marker levels. Minor alleles of 2 of the 5 ATF3 SNPs were associated with decreased CRP levels predominantly in non-obese subjects (Bonferoni P = 0.018, and P = 0.002 for rs11571530, and rs10475, respectively). Two haplotypes inferred from the 5 SNPs, GATTA and TACCA, were also associated with increased or decreased CRP levels, respectively, in non-obese subjects (Bonferoni P = 0.012 and P = 0.01, respectively) but not in obese subjects. Interaction analysis revealed interaction of obesity with an ATF3 genotype associated with a high CRP level (interaction P = 0.006 for SNP rs10475). An effect of obesity on CRP level was also noted in haplotype interaction analysis (interaction P = 0.019 for haplotype TACCA).ConclusionsATF3 polymorphisms are independently associated with CRP levels in Taiwanese subjects. Further, ATF3 genotypes/haplotypes interact with obesity to set CRP levels. These findings may have implications for the prediction of atherosclerotic disease.     

Lack of association between genetic variations in the KALRN region and ischemic stroke

Objectives

To investigate whether KALRN gene variation is associated with ischemic stroke (IS).

Design and methods

Associations to overall IS and IS subtypes were investigated in SAHLSIS, which comprises 844 patients with IS and 668 controls.

Results

Associations between KALRN SNPs and overall IS and cardioembolic stroke were detected. Associations for overall IS were investigated in two additional Swedish samples, but could not be replicated.

Conclusion

KALRN gene variation is not associated with overall IS.     

精神分裂症患者病情与超敏C反应蛋白水平变化关系

目的研究精神分裂症患者病情与超敏C反应蛋白(hs-CRP)水平变化关系。 方法选取2019年4月至2020年4月阳江市公共卫生医院精神科门诊及住院的精神分裂症患者共214例,其中新发或者复发的107例患者为观察组,同期门诊及住院病情稳定的107例患者为对照组。两组患者均采用抗精神病药物治疗,并分别在治疗前和治疗后1个月进行阳性和阴性症状量表(PANSS)评定及检测血清hs-CRP水平,将两组所得数据进行比较,及自身前后对照,并采用Pearson相关分析观察组治疗前后hs-CRP水平与PANSS总分的相关性。 结果观察组治疗前PANSS总分与hs-CRP水平分别为(66.97±9.53)分、8.30(2.10,20.10)mg/L,治疗后PANSS总分与hs-CRP水平分别为(46.48±7.16)分、1.90(0.60,5.20)mg/L。对照组治疗前PANSS总分与hs-CRP水平分别为(30.38±5.34)分、0.90(0.40,2.05)mg/L,治疗后分别为(30.68±2.63)分、1.00(0.40,2.73)mg/L。两组PANSS总分与hs-CRP水平治疗前(t＝33.96,Z＝－7.98)、治疗后(t＝21.02,Z＝－2.49)分别比较,均差异有统计学意义(均P<0.05)。观察组PANSS总分与hs-CRP水平随着病情缓解而明显下降(t＝20.99,Z＝－7.18)(均P<0.01)。相关性分析结果显示,观察组患者血清hs-CRP水平与PANSS总分在治疗前(r₁＝0.73)和治疗后(r₂＝0.41),均呈正相关(均P<0.01)。 结论精神分裂症患者病情轻重与血清hs-CRP水平高低密切相关,hs-CRP检测对动态观察精神分裂症患者病情具有较高的应用价值。     

单纯性肥胖成人血清高敏C反应蛋白、血脂水平与胰岛素抵抗的相关性研究

目的 探讨单纯性肥胖成人血清高敏C反应蛋白(hs-CRP)、血脂水平与胰岛素抵抗(IR)的关系.方法 选择单纯性肥胖成人99例[按体质量指数(BMI)分为i度肥胖组46例,ii度肥胖组38例,iii度肥胖组15例],单纯性超重成人56例及健康成人80例.测定所有入选对象的身高、体质量、腰围、臀围、空腹血糖(FBG)、空腹胰岛素(FIN)、血脂、hs-CRP水平,并计算胰岛素抵抗指数(HOMA-IR)、BMI及腰臀比(WHR).结果 hs-CRP、HOMA-IR、FBG、FIN、TG、TC、LDL-C、脂肪肝发生率随着BMI的升高呈逐渐升高趋势,HDL-C则呈现逐渐降低趋势.血清hs-CRP与BMI、WHR、FIN、HOMA-IR、TG呈显著正相关(P＜0.05～P<0.01),与HDL-C呈显著负相关(P<0.01),多元逐步回归分析提示,BMI、HOMA-IR、HDL-C是影响hs-CRP的独立危险因素.结论 单纯性肥胖成人存在IR,炎性因子hs-CRP的过量表达参与并加重单纯性肥胖成人IR、血脂紊乱的发生和发展.     

C反应蛋白基因多态性与超敏C反应蛋白的关系及其与缺血性脑卒中的关联研究

目的 探讨C反应蛋白(CRP)基因多态性与血浆超敏C反应蛋白(hs-CRP)水平的关系并分析其对缺血性脑卒中(IS)遗传易感性的影响.方法 采用病例对照研究方法,以2008年1月至2010年12月确诊548例急性IS患者为病例组,993例社区人群为对照组.收集年龄、性别等流行病学信息,测量血压,并检测血糖(GLU)、三酰甘油(TC)、胆固醇(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)和血浆hs-CRP浓度.采用聚合酶链反应(Polymerase chain reaction PCR)-限制性内切酶片段长度多态性(Restriction fragment length polymorphism RFLP)的方法进行基因分型.结果 IS组中血浆hs-CRP水平(3.534±3.484) mg/L及hs-CRP升高(≥3.0 mg/L)比例(43.1％)都显著高于对照组[(1.957±2.344) mg/L,16.6％](t=9.475,P＜0.01;x2=128.326,P ＜0.01).CRP基因rs3093059和rs3091244与IS呈负相关,在校正混杂因素后,rs3093059位点相加模型和显性模型的比值比(OR)及其95％可信区间(95％ CI)分别为0.697 (0.528～0.921)、0.671 (0.487～0.923).rs3091244的显性模型的OR值(95％ CI)为0.728(0.536～0.988).在IS组和对照组,CRP基因rs876537、rs3093059、rs3091244都与血浆hs-CRP浓度升高(≥3.0 mg/L)呈正相关(P＜0.05).结论 CRP基因变异与IS呈负相关而与血浆hs-CRP水平升高呈正相关,而hs-CRP水平升高与IS呈正相关,表明血浆hs-CRP水平升高可能是伴随IS而发生.     

血糖水平与超敏C反应蛋白及颈动脉内膜的关系

目的探讨糖代谢和炎性反应与动脉硬化的关系。方法将180例患者通过糖耐量试验分为血糖正常组、糖耐量异常组及2型糖尿病(T2DM)组;每组60例,严格禁食10h后空腹采血,行超敏C反应蛋白(CRP)、一氧化氮(NO)、空腹胰岛素(FIns)及高密度脂蛋白-胆固醇(HDL-C)水平检测及颈动脉内膜—中层厚度(IMT)测定。结果随着血糖异常逐渐加重,超敏CRP逐渐增高,NO、HDL-C及FIns水平呈下降趋势,IMT明显增厚(P<0.05)。结论随着糖代谢异常的加重,体内炎性反应及动脉硬化程度逐渐加重。     

高敏C-反应蛋白与肥胖及非肥胖儿童相关指标关系的探讨

目的了解高敏C-反应蛋白（hs-CRP）在肥胖及非肥胖儿童体内的水平,探讨高敏C-反应蛋白与体重指数（BMI）、临床及实验室相关指标的关系。方法设计两平行组,将114例非肥胖儿童作为对照组,131例肥胖儿童作为研究对象,测量高敏C-反应蛋白水平及相关指标。结果肥胖组高敏C-反应蛋白水平明显高于对照组（P〈0．001）。生化指标空腹血糖和三酰甘油在肥胖组和对照组中有统计学意义（P〈0．01）。高敏C-反应蛋白与BMI之间呈明显相关性（P〈0．05）。结论高敏C-反应蛋白与BMI呈明显正相关;大部分非肥胖儿童的高敏C-反应蛋白浓度不超过2mg／L。     

高敏C反应蛋白在双胍类和磺脲类治疗后的糖尿病患者中的变化

目的探讨炎症因子高敏C反应蛋白(hs-CRP)在使用双胍类和磺脲类联合治疗12周后的2型糖尿病患者中的变化。方法采用免疫比浊法定量检测48例2型糖尿病患者治疗前后hs-CRP的水平,酶法检测空腹血糖(FBG)、血脂,高效液相法检测糖化血红蛋白(HbA1c),比较其治疗前后的变化。结果2型糖尿病患者治疗前后体质量指数(25.62±2.92)vs(25.09±2.98),腰围(85.73±8.66)cm vs(84.75±8.72)cm,FBG(7.92±1.43)mmol/L vs(5.96±1.31)mmol/L,总胆固醇(5.63±1.08)mmol/L vs(4.98±0.79)mmol/L,甘油三酯(2.19±2.09)mmol/L vs(1.58±0.96)mmol/L,低密度脂蛋白胆固醇(3.29±1.17)mmol/L vs(2.91±0.59)mmol/L,hs-CRP(1.66±0.93)mg/L vs(1.20±0.86)mg/L,HbA1c(7.29±1.26)%vs(6.79±0.96)%;上述指标治疗后较治疗前明显下降,其差异有统计学意义(均P<0.01)。结论2型糖尿病患者在血糖、体质量和腰围控制的同时hs-CRP水平降低,hs-CRP可作为临床医生治疗2型糖尿病及其血管并发症时疗效观察的监测指标之一。     

阿司匹林对脑梗死患者血清 C反应蛋白含量的影响及意义

目的:探讨阿司匹林(aspirin,ASP)对脑梗死患者血清C反应蛋白(C-reactiveprotein,CRP)含量的影响,并分析其意义。方法:选择住院及门诊确诊为脑梗死的患者,按照患者基本情况及血清CRP含量抽签法随机分入50,100,300mgASP治疗组,观察在ASP治疗1周及1月后CRP含量的改变。CRP应用TurboxR特定蛋白分析系统(芬兰)以散射比浊法进行测定。结果:脑梗死组患者血清CRP水平均明显增高犤ASP50组为(18.4±6.2)mg/L;ASP100组为(17.8±5.8)mg/L;ASP300组为(19.2±6.3)mg/L犦,与正常对照组(6.1±2.7)mg/L相比,差异有极显著性意义(t=14.165,t=13.812,t=14.227,P<0.001)。应用50mgASP治疗1周及1个月后,血清CRP含量有下降趋势犤分别为(17.4±5.3),(16.5±4.7)mg/L犦,但与治疗前相比差异无显著意义。100mgASP治疗1周后,血清CRP含量有下降趋势(16.7±4.2)mg/L,但与治疗前相比差异无显著性意义;治疗1个月后,血清CRP含量(14.7±3.8)mg/L有显著下降(t=2.175,P<0.05)。300mgASP治疗1周后,血清CRP含量(16.4±3.7)mg/L即有明显下降(t=2.230,P<0.05),治疗1个月后,血清CRP含量有非常显著下降(14.3±4.1)mg/L(t=2.762,P<0.01)。结论:ASP可显著降低脑梗死患者血清CRP含量,其效果呈剂量及时间依赖性。     

急性脑卒中患者血清超敏C反应蛋白水平与卒中后抑郁的相关研究

目的:观察急性脑卒中患者血清超敏C反应蛋白(hs-CRP)水平与卒中后抑郁(PSD)的关系。方法:对46例确诊的急性脑卒中患者采用透射免疫比浊法测定其血清hs-CRP水平,并选择同期无心脑血管意外事件发生史的非脑血管病就诊者24例作对照组。结果:(1)46例急性脑卒中患者3个月PSD发生率为45.7%,其中轻中度抑郁为32.6%,重度为13.0%。(2)卒中后抑郁组及无抑郁组皆较对照组hs-CRP含量增高,对照组含量处于较低水平,且抑郁组明显高于无抑郁组(P<0.01);其中轻中度抑郁组hs-CRP已高于对照组(P<0.05),而重度抑郁组则明显高于无抑郁组及轻中度抑郁组(分别P<0.01,P<0.05)。结论:血清hs-CRP水平与急性脑卒中及并发抑郁障碍关系密切,对早期预测脑卒中后是否并发PSD的判断有一定价值。     

Cross-reactivity between C-reactive protein and idiotypic determinants on A phosphocholine-binding murine myeloma protein

Binding of human 125I-C-reactive protein (CRP) to sheep erythrocytes sensitized with pneumococcal C polysaccharide (E-PnC) was found to be Ca++ dependent and inhibitable by phosphocholine, CRP, and HOPC 8. Binding of 125I-HOPC 8 to EPnC was Ca++ -independent but could also be inhibited by phosphocholine, CRP, and HOPC 8. Thus, CRP and HOPC 8, despite a differential Ca++ requirement, share a common binding specificity for phosphocholine. A monoclonal anti-idiotypic antibody (MAB), GB4-10, prepared in A/J mice immunized with BALB/c HOPC 8 inhibited the binding of both 125I-CRP and 125I-HOPC 8 to E-PnC. In addition, both proteins bound to GB4-10 immobilized on polysterene tubes. Interestingly, binding of 125I-CRP to GB4-10 required Ca++. Similar results were also obtained with another MAB (AB1-2) prepared similarly to GB4-10, whereas neither protein bound to a control MAB (EB3-7) against an alpha1 leads to 3 dextran-binding myeloma protein, J558. Binding of 125I-HOPC 8 to GB4-10 could be inhibited by HOPC 8, keyhole limpet hemocyanin-phosphocholine but not phosphocholine but not phosphocholine, and in the presence of Ca++ by CRP. These data indicate that CRP bears antigenic determinants cross-reacting with certain idiotypic determinants on HOPC 8. They also suggest that Ca++ acts as an allosteric effector, perhaps stabilizing the phosphocholine-binding site of CRP.     

Effect of cardiac resynchronization therapy on cardiac sympathetic nervous dysfunction and serum C-reactive protein level

Background: Cardiac autonomic dysfunction is associated with a poor prognosis in patients with heart failure (HF). Systemic inflammation is elevated in patients with HF. We hypothesized that cardiac resynchronization therapy (CRT) improves cardiac sympathetic nervous dysfunction and systemic inflammation. To test our hypothesis, we evaluated cardiac sympathetic activity and serum levels of high sensitive C‐reactive protein (hs‐CRP) before and after CRT. Methods: Twenty‐seven patients with chronic HF (19 men, eight women; mean age 67 ± 10 years) with nonischemic cardiomyopathy who underwent CRT were evaluated. Each patient was evaluated before and 6 months after CRT. Responders were defined as patients showing ≥15% absolute decrease in left ventricular end‐systolic volume. Cardiac sympathetic activity was estimated with cardiac ¹²³I‐metaiodobenzylguanidine (MIBG) scintigrams. Results: Patients were categorized as responders (n = 19) and nonresponders (n = 8) according to echocardiographic findings. In responders, the mean heart‐to‐mediastinum (H/M) ratio at the delayed phase in cardiac ¹²³I‐MIBG scintigraphic findings was significantly increased (P < 0.05) and serum levels of hs‐CRP were decreased (P <0.01). Such improvements were not observed in nonresponders. Stepwise multiple regression analysis showed that the reduction in hs‐CRP level was independently associated with the increase in the H/M ratio at delayed phase. Conclusions: Our results demonstrated that cardiac sympathetic nervous dysfunction and systemic inflammation were improved in responder HF patients to CRT. Furthermore, the reduction in systemic inflammation was associated with the improvement in cardiac sympathetic nervous dysfunction. (PACE 2011; 34:1225–1230)     

Correlations between serum amyloid A protein and C-reactive protein in infectious diseases

Serum amyloid A (SAA) protein is an acute phase reactant that has recently become of increasing interest as a marker for disease and treatment monitoring. We have correlated SAA levels to those of C-reactive protein (CRP) in sera from 98 patients admitted to an infectious diseases clinic because of viral and bacterial infections, including hepatitis A and B, cytomegalovirus infection, varicellae-zoster, infectious mononucleosis, influenza A, bacterial pneumonia, streptococcal pharyngitis, bacterial sepsis and severe bacterial sepsis. The study population was chosen from the clinical setting as representatives of these frequently encountered patient groups. SAA levels correlated significantly with CRP levels (r2=0.757, p<0.001) for the entire studied population. Furthermore, positive correlations were found in viral (r2=0.572, p<0.001) and bacterial (r2=0.666, p<0.001) infections. Positive correlations were also observed when the values were compared in accordance with CRP levels higher and lower than 100 mg/L (r2=0.689, p<0.001; CRP>100; r2=0.397, p<0.001; CRP<100). Because SAA is more sensitive than CRP for the detection of minor inflammatory stimuli, as in the viral and low CRP groups, we conclude that SAA can be of use in several viral infections, as well as in non-invasive and early invasive bacterial infections.     

麻疹患者血清C-反应蛋白水平与发病年龄的相关性分析

目的 分析麻疹患者C-反应蛋白（CRP）水平与发病年龄的关系。方法 收集有麻疹临床症状和体征、麻疹病毒IgM抗体阳性的442例麻疹患者血清标本,采用免疫散射比色法测定血清CRP。结果 47．7％（211／442）的麻疹患者显示CRP水平升高。麻疹患者CRP水平及其异常率随年龄的增加而升高,相关系数（r）分别为0．6804（P〈0．01）和0．6314（P〈0．01）;在剔除了白细胞（WBC）异常升高的病例后,r分别为0．7010（P〈0．01）和0．6496（P〈0．01）。其中15岁以上麻疹患者CRP的异常率（84．5％）明显高于15岁以下的患者（17．4％,P〈0．01）。结论 麻疹患者出现高比例的CRP升高,且其CRP水平及异常率与发病年龄呈正相关。     

Association between genetic polymorphisms of the NPHS1 gene and membranous glomerulonephritis in the Taiwanese population

BackgroundMembranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in adults. NPHS1 encoding nephrin is a transmembrane protein of the immunoglobulin family. We clarified the relationship between NPHS1 gene polymorphisms and the susceptibility or progression of MGN.MethodsWe recruited a cohort of 132 biopsy-diagnosed MGN patients and 257 healthy subjects. Genotyping of three SNPs (rs401824, rs437168 and rs3814995) at chromosome positions 41034749 (5′UTR), 41026259(exon17) and 41034052 (exon 3) was performed using a Taqman SNP genotyping assay.ResultsThere was a significant difference in genotype frequency distribution of rs437168 polymorphism between MGN patients and controls. The results also showed that the frequency of the G allele was significantly higher in the patient group. Among the polymorphisms rs437168, rs401824 and rs3814995, no significant haplotype was shown in MGN patients. A stratified analysis revealed that a high disease progression in the AA genotype of rs401824 and GG genotype of rs437168 patients were associated with a low rate of remission.ConclusionsThe presence of the different genotypes of NPHS1 was associated with susceptibility of MGN and the remission of proteinuria during disease progression after the therapy.     

原发性高血压患者发病与线粒体DNA控制区基因变异的关系

目的:探讨原发性高血压患者线粒体DNA控制区基因变异,并评估其在高血压发病中的作用。方法:提取符合WHO高血压诊断标准的20例原发性高血压患者和20例正常血压者的DNA。用3对交叉重叠引物扩增全部线粒体控制区D环基因,进行直接基因测序和对比分析。结果:原发性高血压患者线粒体D环控制区的变异频率及密度犤13.95个/例,0.19/(100个碱基·例)犦均高于正常血压组犤10.7个/例,0.14/(100个碱基·例犦χ2=11.84,P<0.01)。线粒体转录因子结)(合位点1区域呈高变异状态,而且存在部分微卫星区的不稳定,np152C及np16189C的多态性变化可能为高血压的高风险位点。结论:原发性高血压患者D环区基因高变异率,线粒体DNA控制区变异可能与高血压的发病存在密切的关联。     

麻疹患者血清C-反应蛋白水平与发病年龄的相关性分析

目的分析麻疹患者C-反应蛋白(CRP)水平与发病年龄的关系。方法收集有麻疹临床症状和体征、麻疹病毒IgM抗体阳性的442例麻疹患者血清标本,采用免疫散射比色法测定血清CRP。结果47.7%(211/442)的麻疹患者显示CRP水平升高。麻疹患者CRP水平及其异常率随年龄的增加而升高,相关系数(r)分别为0.680 4(P<0.01)和0.631 4(P<0.01);在剔除了白细胞(WBC)异常升高的病例后,r分别为0.701 0(P<0.01)和0.649 6(P<0.01)。其中15岁以上麻疹患者CRP的异常率(84.5%)明显高于15岁以下的患者(17.4%,P<0.01)。结论麻疹患者出现高比例的CRP升高,且其CRP水平及异常率与发病年龄呈正相关。