血清淀粉样蛋白A1基因多态性对汉族人群颈动脉内中膜厚度的影响

目的 探讨血清淀粉样蛋白A1(SAA1)基因多态性对颈动脉内中膜厚度(IMT)的影响.方法资料来源于2007至2010年"新疆维吾尔自治区不同民族心血管疾病危险因素调查研究"数据,人选其中健康汉族人群449例,采用限制性片段长度多态性(RFLP)方法对SAA1基因rs2229338和rs12218进行分型.彩色超声检测颈总动脉干部内中膜厚度(CC-IMT)和膨大部内中膜厚度(CB-IMT),分析不同基因型之间颈动脉IMT的差异.结果 (1)rs2229338和rs12218存在强连锁不平衡(D'=0.89).(2)SAA1基因rs2229338突变型(GG+AG)与野生型(AA)的CC-IMT和CB-IMT值差异均无统计学意义.(3)SAA1基因rs12218突变型(CC+CT)CC-IMT值大于野生型(TT)[(0.081±0.071)cm比(0.068±0.019)cm,P=0.01],在校正年龄、性别、血压、腰围、肌酐和高密度脂蛋白胆固醇的影响后,差异仍具有统计学意义(P=0.04);rs12218突变型(CC+CT)与野生型(TT)的CB-IMT值差异无统计学意义[(0.085±0.038)cm比(0.081±0.052)cm,P=0.36].结论在新疆维吾尔自治区汉族人群,SAA1基因多态性和颈动脉IMT存在关联,rs12218突变型基因可能会增加颈动脉IMT.

Abstract：

Objective To explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang. Methods A total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography. Results (1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D'=0. 89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT[(0.081 ±0.071)cm vs (0.068 ±0. 019 ) cm, P = 0. 01] was significantly thicker in CC + CT genotype ( mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age,gender,blood pressure, waist circumference, creatinine and high density lipoprotein cholesferoL CB-IMT [(0.085±0. 038)cm vs. (0.081 ± 0. 052) cm,P =0. 36] was similar between CC +CT genotype and TT genotype of rs12218 groups. Conclusion Our results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.     

血清淀粉样蛋白A1基因多态性对汉族人群颈动脉内中膜厚度的影响

Objective To explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang. Methods A total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography. Results (1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D'=0. 89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT[(0.081 ±0.071)cm vs (0.068 ±0. 019 ) cm, P = 0. 01] was significantly thicker in CC + CT genotype ( mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age,gender,blood pressure, waist circumference, creatinine and high density lipoprotein cholesferoL CB-IMT [(0.085±0. 038)cm vs. (0.081 ± 0. 052) cm,P =0. 36] was similar between CC +CT genotype and TT genotype of rs12218 groups. Conclusion Our results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.     

Klotho基因G-395A多态性与华中地区老年汉族人群颈动脉内中膜厚度的相关性

目的探讨Klotho基因G-395A位点多态性与华中地区老年(年龄≥60岁)汉族人群颈动脉内中膜厚度(IMT)的相关性。方法随机选取278例华中地区老年汉族患者,根据IMT分为IMT增厚组(IMT≥1 mm,132例)和对照组(IMT1 mm,146例),分别检测各组血压、血糖、血脂等生化指标,并用Taq Man基因探针法检测各组Klotho基因G-395A位点的基因型。结果与对照组相比,IMT增厚组GG基因型和G等位基因频率明显增高,AA基因型和A等位基因频率明显降低,AG基因型无明显差异。经多元Logistic回归分析后,G等位基因频率与IMT增厚存在相关性,为IMT增厚的独立危险因子。结论 Klotho基因G-395A位点多态性与华中地区老年汉族人群颈动脉IMT具有相关性,G-395A多态性有可能作为颈动脉IMT增厚的预测指标之一。     

血清淀粉样蛋白A水平及其基因多态性与特发性静脉血栓栓塞症的相关性研究

目的:探讨血清淀粉样蛋白A(SAA)水平及其基因多态性与维、汉族特发性静脉血栓栓塞症(VTE)之间的关系。方法:采用病例-对照研究,选择维族VTE162例、汉族VTE184例,性别和年龄匹配的健康体检者维族203例、汉族230例,应用ELESA法检测SAA水平、PCR-PFLP技术检测SAA基因rs12218和rs4638289多态性。结果:维、汉民族VTE患者吸烟所占比例均较高,经回归分析得出,吸烟是VTE的独立危险因素。维吾尔族VTE组的体质指数(BMI)为[(27.7±4.1)vs.(25.8±4.2)kg/m~2]、腰围[(85.1±9.6)vs.(81.5±9.9)cm]高于对照组,且差异有统计学意义(P0.05);而汉族VTE组的腰围[(83.3±10.1)vs.(80.0±10.6)cm]高于对照组,且差异有统计学意义(P0.05),而BMI[(24.9±3.6)vs.(24.5±3.4)kg/m~2]在两组间无差别;腹型肥胖是维、汉族VTE患者的危险因素。汉族人群中,VTE组的C反应蛋白(CRP)高于正常对照组(5.06 vs.3.64 mg/L),且差异有统计学意义[(P0.05),校正后,CRP是VTE的独立危险因素。维、汉族VTE组的SAA水平均升高,分别为(6.3±2.9)vs.(5.5±2.4)mg/L和(8.3±3.7)vs.(6.8±3.3)mg/L,P0.05],经回归分析显示SAA水平不是维、汉族VTE的独立危险因子。SAA基因rs12218和rs4638289多态性在维、汉民族中的分布不存在民族异质性;SAA基因rs12218和rs4638289多态性在VTE组和正常对照组分布差异无统计学意义,均不是VTE的危险因子。结论:腹型肥胖、吸烟是维、汉族VTE共同的危险因素;CRP水平是汉族VTE的危险因素;VTE患者的SAA水平升高,但不是维、维汉族VTE的独立危险因素,且SAA基因多态性不是特发性VTE的危险因素。     

2型糖尿病血清淀粉样蛋白A水平与颈总动脉内中膜厚度相关

169 例短病程2型糖尿病患者,根据大动脉内中膜厚度(IMT)分为动脉粥样硬化(AS)组和非AS组,测定血清淀粉样蛋白A(SAA)水平,结果显示2型糖尿病组SAA水平较对照组高,AS组高于非AS组,并与年龄、体重指数、腰臀比及颈总动脉IMT呈正相关;年龄、C反应蛋白及SAA是影响颈总动脉IMT的相关因素.     

血清淀粉样蛋白A和血清淀粉样蛋白A-低密度脂蛋白复合物与冠心病的临床研究

目的探讨血清淀粉样蛋白A(SAA)和SAA-LDL复合物与冠状动脉病变程度和心肌缺血时心功能状态之间的关系。方法选择冠心病患者93例,行冠状动脉造影时根据Gensini评分进行分组:20分为A组(32例),20～40分为B组(30例),40分为C组(31例)。经冠状动脉造影排除冠心病者30例作为对照组。测定空腹血脂、血糖,采用ELISA法测定血清SAA和SAA-LDL复合物的水平。结果 Pearson相关和多元线性回归分析显示,Gensini评分与LVEF呈负相关,与血清SAA-LDL复合物水平呈正相关,与SAA、血脂、血糖水平不相关;LVEF与SAA-LDL复合物水平呈负相关,与SAA、血脂、血糖水平不相关。单因素方差分析显示,与对照组和A组比较,B组和C组lgSAA-LDL明显升高;与B组比较,C组lgSAA-LDL明显升高(P0.05);而对照组与A组lgSAA-LDL比较差异无统计学意义(P0.05)。结论血清SAA-LDL复合物比SAA更敏感地反映心肌缺血的严重程度及心肌缺血后心脏收缩功能的状态,严重的心肌缺血可导致左心室收缩功能障碍。     

老年脑梗死患者血清P-选择素及淀粉样蛋白A与颈动脉粥样硬化相关性

颈动脉粥样硬化性狭窄已成为老年脑梗死独立危险因素,血清P-选择素(P-selectin,Ps)作为血小板活化的标志及炎症反应的介质,在介导动脉粥样硬化形成、发展的各个时期中发挥了主要作用[1].血清淀粉样蛋白A(SAA)为急性炎症反应时的一种主要时相蛋白,研究发现其在糖尿病患者的肾血管病变过程中发挥重要作用[2].最近研究表明,Ps和SAA与冠状动脉硬化发病密切相关[3].本研究对合并颈动脉狭窄的老年脑梗死患者的Ps和SAA进行检测,分析其与颈动脉粥样硬化的关系.     

急性时相血清淀粉样蛋白A与2型糖尿病颈动脉粥样硬化的关系

目的 探讨2型糖尿病患者急性时相血清淀粉样蛋白A与颈动脉粥样硬化的关系.方法 49例2型糖尿病患者根据颈动脉内中膜厚度(IMT)及斑块分为颈动脉粥样硬化组和无颈动脉粥样硬化组.空腹抽血测糖化血红蛋白(HbAlc)、血脂和炎症细胞因子.结果 颈动脉粥样硬化组C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)比无颈动脉粥样硬化组显著升高(P<0.01).颈动脉粥样硬化组高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A-1(ApoA-1)显著降低(P<0.05)和甘油三脂(TG)显著升高(P<0.05)于无颈动脉粥样硬化组.Spearman相关分析显示,BMI、腰围与SAA、IL-6呈显著正相关(P<0.01),与CRP、TNF-α元显著相关性.SAA与TNF-α(P<0.01)、IL-6(P<0.01)显著正相关,而与CRP无相关性.结论 伴有颈动脉粥样硬化的2型糖尿病患者炎症细胞因子血清淀粉样蛋白A明显升高.炎症细胞因子SAA与肥胖和颈动脉粥样硬化密切相关.     

血清淀粉样蛋白A对脑动脉粥样硬化性狭窄影响的研究进展

血清淀粉样蛋白A（serum amyloid A，SAA）存在于各种哺乳动物和禽类的体内，其合成的部位主要在肝脏，由同一簇基因编码的一组多形性蛋白组成。SAA家族包含不同表达形式的载脂蛋白、急性相蛋白A（acute—phase serum amyloid A，A—SAA）和结构型SAA（constitutive serum amyloid A，C—SAA）。正常人血清SAA值为0—0．78mg／L。当机体受到各种炎性反应因素刺激时，     

血清淀粉样蛋白A的研究进展

血清淀粉样蛋白A(SAA)是一个非常敏感的急性相反应物。不管是在健康人还是在患有冠状动脉疾病的人群中,SAA、C反应蛋白等炎症反应物均能预测心血管事件发生的危险几率。     

高血压患者血清瘦素、抵抗素水平与颈动脉内膜-中层厚度的关系

目的:探讨原发性高血压患者血清瘦素、抵抗素水平的变化及与颈动脉粥样硬化的相关关系.方法:入选80例原发性高血压患者(病例组),另选32例健康对照者.采用酶联免疫吸附法检测血清瘦素、抵抗素水平;采用彩色超声诊断仪测定颈动脉内膜-中层厚度(IMT).结果:病例组的瘦素(t=-2.530,P=0.013)和抵抗素水平(t=-2.077,P=0.041)均高于对照组.病例组的颈动脉IMT(t=-3.115,P=0.003)和颈动脉最大IMT(t=-3.271,P=0.002)均大于对照组.Pearson相关分析示,高血压患者血清瘦素与IMT(r=0.311,P=0.012)和最大IMT(r=0.308,P=0.013)呈显著正相关;血清抵抗素与IMT(r=0.335,P=0.006)和最大IMT(r=0.284,P=0.022)呈显著正相关.结论:原发性高血压患者的血清瘦素、抵抗素水平显著升高,且它们和颈动脉IMT存在相关性.     

Correlation between serum YKL-40 and carotid intima media thickness in type 1 diabetics

It has been suggested that elevated serum level of YKL-40 could be a risk factor as well as early marker of both type 2 and type 1 diabetes mellitus (T1D) and their complications. We investigated the correlation between serum level of YKL-40 and carotid intima media thickness (cIMT) as well as urinary albumin/creatinine ratio (UACR) in type 1 diabetic patients. A total of 49 patients with T1D and 43 healthy controls underwent the assessment of serum level of YKL-40 (by ELISA) and cIMT measurement (by Doppler ultrasonography). Fasting blood and urine samples were also taken to measure the levels of hemoglobin A1C, lipid profile, CBC, serum and urine creatinine, and urine albumin. Serum levels of YKL-40, cIMT, and UACR were significantly higher in diabetic patients compared to those in healthy people (P < 0.001). Serum levels of YKL-40 had a significant correlation with cIMT, and duration of diabetes. We report that YKL-40 may be a good prognostic as well as diagnostic marker of early macrovascular complications in T1D.

     

Analysis of serum amyloid A in sarcoidosis patients

A crucial pathogenetic role of serum amyloid A (SAA) in granulomatous inflammation of sarcoidosis has recently been reported. In this study we analyzed SAA expression in detail, starting from proteomic analysis of serum of sarcoidosis patients. We also used the faster ELISA method that enabled us to examine a greater number of samples. Serum concentrations of SAA were significantly higher in sarcoidosis patients than controls (p<0.001), inversely correlated with FEV(1) and significantly higher in patients with subacute onset requiring prolonged and multiple steroid treatments (class 6 SCAC) than in patients with subacute onset not requiring therapy (class 4 SCAC) (p<0.001). Our results suggest that serum amyloid A could be a suitable marker of sarcoidosis: its serum concentrations are significantly higher in sarcoidosis patients than controls, the protein is only expressed in gels of sarcoidosis patients and not in healthy subjects, and the SAA1 isoforms could match the unidentified biomarker of sarcoidosis reported in a previous proteomic study by another group. The effectiveness of SAA as a clinical biomarker of sarcoidosis should now be investigated in a large prospective study.     

Evaluation of intima media thickness of the common and internal carotid arteries with inflammatory markers in familial Mediterranean fever as possible predictors for atherosclerosis

The aim of the present study was to determine whether intima-media thickness (IMT) of the common (CCA) and internal carotid arteries (ICA) was increased due to chronic inflammation occurring in familial Mediterranean fever (FMF) patients compared to healthy controls. Erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), serum amyloid A protein (SAA), lipid profile and homocysteine levels were examined in 70 FMF patients [median age 14 years (range 4–24)] in an attack free period and in 50 healthy controls [median age 14 years (range 4–18)]. All the patients were homozygous or compound heterozygous for MEFV mutations. IMT of both CCA and ICA was evaluated with a high resolution B-mode ultrasonography. ESR, CRP, fibrinogen and SAA levels were significantly higher in FMF patients as compared to healthy controls (P < 0.05). Intima media thickness of the common carotid artery was found to be significantly higher in FMF patients when compared to those in healthy controls [0.37 mm (0.26–0.61) vs. 0.28 mm (0.21–0.35), P < 0.001]. The median ICA-IMT was significantly increased in the patients when compared to those in the controls [0.25 mm (0.18–0.44) vs. 0.22 mm (0.10–0.26), P < 0.001]. A positive correlation between CCA-IMT and SAA levels (r = 0.24, P = 0.04) was found while ICA-IMT positively correlated with ESR (r = 0.31, P = 0.008) and fibrinogen levels (r = 0.30, P = 0.012). Intima media thickness, an early predictor of atherosclerosis, may be associated with subclinical inflammation in children with FMF. Further studies will enlighten whether these patients will be predisposed more to coronary artery disease. Yelda Bilginer and Fatih Ozaltin contributed equally to this work.     

Differential affinity of serum amyloid A1 isotypes for high-density lipoprotein

Serum amyloid A (SAA), a precursor of reactive amyloid deposits, is a multigene product. SAA1, predominant both as an amyloid precursor and in plasma, consists of three allelic variants (SAA1.1, SAA1.3, and SAA1.5). Several investigations have shown that the SAA1.3 allele is associated with susceptibility to AA-amyloidosis in Japanese, and the SAA1.5 allele is related with higher serum concentrations of SAA. However, these results have not been interpreted functionally. This study assessed the affinity of SAA isotypes for high-density lipoprotein (HDL), to which SAA binds in plasma. Using a surface plasmon resonance-based apparatus (BIAcore), the affinity between immobilized recombinant human SAAs and HDL was determined. The SAA concentration was measured in fractions after ultracentrifugation (d?=?1.23) of sera from patients with rheumatoid arthritis, whose SAA1 genotypes were determined. In the BIAcore analysis, as the dissociation reaction under the conditions used was too rapid to fit the typical kinetic model, the steady-state affinity model was used. The affinity (kd) of SAA1.1, SAA1.3, and SAA1.5 for HDL was 1.4?×?10^?5, 1.8?×?10^?5, and 3.7?×?10^?6, respectively. rSAA1.5 showed significantly (p?<?0.05) stronger affinity than the other two. The fraction of lipid-free SAA in serum was significantly (p?<?0.001) lower in the patients with larger numbers of the 1.5 allele at the SAA1 locus. These results suggest that the relatively high affinity of SAA1.5 may cause the high serum concentration and may be related to the low susceptibility to amyloidosis.     

冠心病血清超敏C-反应蛋白和血清淀粉样蛋白A，脂联素的关系

摘要：目的：探讨冠心病（CHD）患者血清超敏C-反应蛋白（hs-CRP）、血清淀粉样蛋白A（SAA）和血清脂联素（APN）的关系。方法：人选确诊冠心病的患者66例（CHD组）,正常者20例（正常对照组）。分别测定其血清hs—CRP、SAA、APN水平,并进行比较。结果：CHD组hs—CRP、SAA水平分别为（2．88±0．61）mg／L和（9．89±5．23）mg／L,明显高于正常对照组的（0．67±0．17）mg／L和（1．27±1．11）mg／L,P均〈0．01;CHD组APN水平为（3．38±0．26）μg／L,显著低于正常对照组的（3．91±0．34）／Lg／L,P〈0．05。hs—CRP水平与SAA水平呈正相关（r=0．835,P〈0．05）,与APN水平呈负相关（r=-0．285,P〈0．05）。结论：CHD患者血清hs—CRP、血清淀粉样蛋白A水平明显升高,血清脂联素水平明显降低,血清hs—CRP水平与淀粉样蛋白A水平呈正相关,与脂联素水平呈负相关,可作为临床诊断和预后判断的依据。