苏州地区健康人群β-纤维蛋白原-455G/A、-148C/T基因多态性频率及与血浆纤维蛋白原水平的关系

目的调查分析苏州地区健康人群β-纤维蛋白原-455G/A、-148C/T基因位点的多态性分布情况.方法用clauss法测定血浆纤维蛋白原浓度,应用多聚酶链反应限制性酶切法,分析102名健康人DNA样品的基因型,计算等位基因频率.结果 Fgβ-455G/A多态性中,突变位点A等位基因频率为0.186,β-148C/T多态性中,T等位基因频率为0.206.A或T基因携带者血浆Fg水平明显高于非携带者.结论苏州地区人群Fg等位基因频率低于广东地区.β-455G/A、β-148C/T基因多态性与血浆Fg水平相关.     

冠心病多位点β纤维蛋白原基因多态性检测的临床意义

目的研究纤维蛋白原(Fg)Bβ基因多个位点的多态性与血浆水平及冠心病的关系。方法运用聚合酶链反应-限制性片段长度多态性分析技术及核苷酸序列测定鉴定FgBβ基因中7个可能与血栓相关的多态性位点:-β148C/T-、249 C/T3、45 C/T、-455G/A-、854 G/A、1689T/G及Bc1 I G/A;比浊法测定血浆纤维蛋白原水平。结果与正常对照组相比,冠心病组血浆Fg显著升高(P<0.05);有-148C/T-、455G/A、-854G/A或Bc1 I G/A基因多态性变异组,其血浆Fg水平高于无变异组(P<0.05),其中,同时携带A-455、A-854者增高更为显著(P<0.01)。冠心病组A-455、T-148基因型频率(0.334)显著高于高血压组(0.196)和正常对照组(0.195),多态性位点G-455、C-148或A-455、T-148分别紧密连锁,符合率超过97%;Logistic回归分析发现,携带FgB-β148T-、455A基因的高血压患者,患冠心病的危险性是非携带者的1.654倍(P=0.01,95%CI:1.207-2.267)。结论FgBβ基因多态性与血浆Fg水平及缺血性心脏病发生的危险性相关;选择性FgBβ基因多态性位点的检测有助于临床上冠心病易患人群的筛查。     

纤维蛋白原β-455G/A、-148C/T、448G/A基因多态性与血浆纤维蛋白原水平的关系

目的　调查 15 6名广东汉族健康人纤维蛋白原 (Fg) β - 45 5G/A、- 148C/T、44 8G/A基因多态性频率分布、连锁不平衡关系及与血浆Fg水平的关系。方法　用限制性片段长度多态性 (RFLP)分析方法和比浊法检测血浆Fg水平。结果　等位基因A-4 55、T-14 8和A4 48的频率分别是 0 .2 76 ,0 .2 85及 0 .2 72。 15 6人中 3个多态性位点G-4 55、C-14 8和G4 48或A-4 55、T-14 8和A4 48分别紧密连锁 ,符合率超过97%。 3个多态性位点携带及不携带突变基因两组血浆Fg水平分别是 β - 45 5 :(3 .13± 0 .74)g/L和(2 89± 0 .5 7)g/L ;β - 148:(3 .12± 0 .73)g/L和 (2 .89± 0 .5 8)g/L ;β 44 8:(3 .13± 0 .74)g/L和 (2 89±0 5 7)g/L。上述 3个位点携带突变基因组血浆Fg水平均比野生型组明显升高 (P <0 .0 5 )。结论　 3对等位基因紧密连锁不平衡 ,携带突变基因者较不携带者血浆Fg水平高 ,提示Fgβ - 45 5G/A、- 148C/T、44 8G/A 3种基因多态性均与血浆Fg水平关联     

纤维蛋白原紧密连锁不平衡基因位点BβG/A-455、C/T-148、G/A+448与缺血性脑血管病相关性分析

目的 分析纤维蛋白原(FIB)3个紧密连锁不平衡基因位点BβG/A-455、C/T-148、G/A+448基因多态性及血浆FIB水平与缺血性脑血管病的相关性.方法 以我院2010年2月至2012年2月收治的缺血性脑血管病患者89例为病例组,以同期在我院健康体检的50例为对照组,检测两组血浆FIB水平,使用多聚酶链式反应限制性片段长度多态性(PCR-RFLP)技术测定BβG/A-455、C/T-148、G/A+448基因片段.结果 缺血性脑血管病患者中,FIB基因型分布、BβA-455、T-148、A+448等位基因频率与对照组比较差异有统计学意义(P＜0.05).两组血浆FIB水平比较差异有统计学意义(P＜0.01),病例组高于对照组.A、T等位基因携带者与非携带者血浆FIB水平比较差异有统计学意义(缺血性脑血管病患者组,P＜0.01;对照组,P＜0.05),携带者高于非携带者.结论 FIB 3个紧密连锁不平衡基因位点BβG/A-455、C/T-148、G/A+448基因多态性及血浆FIB水平与缺血性脑血管病呈明显的正相关,BβG/A-455、C/T-148、G/A+448基因多态性可能是缺血性脑血管病的遗传易感因素.     

β—纤维蛋白原—455G／A基因多态性对缺血性脑卒中患者血浆纤维蛋白原水平的影响

为了分析β-纤维蛋白原-455G/A(β-Fg-455G/A)基因多态性与环境因素对血浆Fg水平及缺血性脑卒中发病的影响,应用聚合酶链反应(PCR)及限制性内切酶分析的方法,分析了104例缺血性脑卒中患者及156例健康人的β-Fg-455G/A基因多态现象,用比浊法测定血浆Fg水平.研究结果显示,病例组血浆Fg水平明显高于对照组(P＜0.01).无论男、女患者与对照相比,A等位基因携带者血浆Fg水平均比同组GG基因型者明显升高(P＜0.05).对照组内只有A等位基因携带者随年龄增长血浆Fg水平有明显升高(P＜0.05).病例组男性按吸烟及基因型情况分组,在GA基因型中,吸烟组血浆Fg水平高于不吸烟与戒烟组(P＜0.05);GG基因型组吸烟与否对Fg水平无显著影响(P＞0.05).病例组与对照组A等位基因频率分布无差异.结论提示,A等位基因携带者血浆Fg水平升高,并随年龄、吸烟而更加显著,提示β-Fg-455 A等位基因携带者血浆Fg水平更易受环境因素影响而升高,故此基因多态性可用于易感人群的检测,对缺血性脑卒中早期防治有一定意义.     

Fg β-148 C/T基因多态性对缺血性脑卒中患者血浆Fg水平的影响

目的分析纤维蛋白原(Fg)β-148 C/T基因多态性与性别、年龄、吸烟等因素对血浆Fg水平的影响.方法用PCR-RFLP的方法分析基因多态性,比浊法测定血浆Fg水平.结果病例组血浆Fg水平明显高于对照组(P＜0.01),两组的T1a基因频率分布差异无显著性(P＞0.05).男女两性的血浆Fg水平比较差异无显著性(P＞0.05);两性中T-148基因携带者血浆Fg水平均比CC基因型者明显升高((P＜0.05).在T-14携带者中,血浆Fg水平随年龄增长而升高(P＜0.05);吸烟组Fg水平高于不吸烟与戒烟组(P＜0.05).结论Fgβ-148 C/T基因多态性与血浆Fg水平相关,T-1a基因携带者更易受年龄、吸烟等因素影响使血浆Fg水平升高.提示Fgβ-148 C/T基因多态性可作为血栓性疾病的遗传易感标志之一.     

对氧磷酶2 311和纤维蛋白原β-455基因多态性与动脉粥样硬化性血栓性脑梗死的相关性

目的 探讨对氧磷酶2（PON2）311、纤雏蛋白原β链（Fgβ）-455基因多态性与动脉粥样硬化性血栓性脑梗死（ACD的关系。方法 采用病例．对照研究方法，应用聚合酶链反应、聚合酶链反应．限制性片段长度多态性技术对108例ACI患者、75例无栓对照者及123例正常对照者的PON2 C311S和Fgβ-455G／A基因多态性进行检测，分析其基因型和等位基因频率。结果 ACI患者中PON2 311C等位基因频率显著高于正常人（P=0．0007），可能影响了该酶蛋白的功能；ACI患者中Fgβ-455A等位基因频率显著高于正常人（P=0．0464），可能影响了血浆纤雏蛋白原的功能。结论 PON2第9外显子311C等位基因和Fgβ-455A等位基因与脑梗死的发生相关。     

β-纤维蛋白原-455 G/A基因多态性与脑梗死的关系

目的:探讨β-纤维蛋白原-455 G/A(-βFg-455G/A)基因多态性与中国东北地区汉族脑梗死发病(CI)的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测脑梗死组(CI组)72例和对照组69例-βFg-455G/A基因的多态性,并测定其血浆纤维蛋白原(Fg)的含量。结果:经χ2检验,各基因型频率和等位基因频率在两组间均无显著性差异(P>0.05);CI组血浆Fg水平(2.70±1.05 g/L)和对照组(2.62±0.51 g/L)比较差异无显著性意义(P>0.05)。结论:本研究未发现-βFg-455G/A基因多态性与脑梗死之间存在相关关系。     

β—纤维蛋白原—455G／A基因多态性的研究进展

多篇流行病学调查报道血浆纤维蛋白原（Fg)水平与心脑血管疾病，静脉血栓形成以及外周动脉性疾病强相关，而β-纤维蛋白原-455G/A基因多态性可导致血浆纤维蛋白原水平增高，从而引起高凝状态，致使血栓发病率升高。本文综述了近年来关于β-纤维蛋白原-455G/A基因多态性的研究进展。     

β-纤维蛋白原-455 G/A基因多态性对缺血性脑卒中患者血浆纤维蛋白原水平的影响

为了分析 β 纤维蛋白原 4 5 5G A(β Fg 4 5 5G A)基因多态性与环境因素对血浆Fg水平及缺血性脑卒中发病的影响 ,应用聚合酶链反应 (PCR)及限制性内切酶分析的方法 ,分析了 10 4例缺血性脑卒中患者及 15 6例健康人的 β Fg 4 5 5G A基因多态现象 ,用比浊法测定血浆Fg水平。研究结果显示 ,病例组血浆Fg水平明显高于对照组 (P <0 .0 1)。无论男、女患者与对照相比 ,A等位基因携带者血浆Fg水平均比同组GG基因型者明显升高 (P <0 .0 5 )。对照组内只有A等位基因携带者随年龄增长血浆Fg水平有明显升高 (P <0 .0 5 )。病例组男性按吸烟及基因型情况分组 ,在GA基因型中 ,吸烟组血浆Fg水平高于不吸烟与戒烟组 (P <0 .0 5 ) ;GG基因型组吸烟与否对Fg水平无显著影响 (P >0 .0 5 )。病例组与对照组A等位基因频率分布无差异。结论提示 ,A等位基因携带者血浆Fg水平升高 ,并随年龄、吸烟而更加显著 ,提示 β Fg 4 5 5A等位基因携带者血浆Fg水平更易受环境因素影响而升高 ,故此基因多态性可用于易感人群的检测 ,对缺血性脑卒中早期防治有一定意义     

纤维蛋白原β—455G／A,—148C／T,448G／A基因多态性与血浆纤 …

目的调查１５６名广东汉族健康人纤维蛋白原（Ｆｇ）β－４５５Ｇ／Ａ、－１４８Ｃ／Ｔ、４４８Ｇ／Ａ基因多态性频率分布、连锁不平衡关系及与血浆Ｆｇ水平的关系。方法用限制性片段长度多态性（ＲＦＬＰ）分析方法和比浊法检测血浆Ｆｇ水平。结果等位基因Ａ＾－４５５、Ｔ－１４８和Ａ＾４４８的频率分别是为０．２７６,０．２８５及０．２７２。１５６人中３个多态性位点Ｇ＾－４５５、Ｃ＾－１４８和Ｇ＾４４８或Ａ＾－４５５、     

纤维蛋白原Bβ链基因多态性与其含量、分子活性及脑梗死的关系

论 FgBβBcl-1等位基因A及其变异型人群是脑梗死的易感人群;FgBβ-854是Fg浓度和分子聚合活性的主要调控位点之一.     

AMI is associated with polymorphisms in the NOS3 and FGB but not in PAI-1 genes in young adults

BACKGROUND: We investigated the relationship between NOS3, FGB and PAI-1 polymorphisms and endothelial dysfunction and risk factors for acute myocardial infarction (AMI) in young adults. METHODS: Endothelial function was measured by response to flow mediated vasodilation (FMV) and induced by nitrate (FMN). Biochemical parameters were measured by standard enzymatic methods and plasma total nitrate was analyzed by the NOA system. NOS3 (T-786C, G894T and intron 4A/B STR), FGB (C-148T and G-455A) and PAI-1 (4G/5G) polymorphisms were determined by PCR-RFLP. RESULTS: Concentrations of total and LDL cholesterol, apo B, triglycerides, nitrate, PAI-1 and fibrinogen were higher and apo AI, HDL cholesterol and FMV were lower in AMI patients than in controls (p<0.001). PAI-1 (p<0.001) but not nitrate was higher in AMI patients with low response to FMV. NOS3 T-786C and FGB C-148T polymorphisms were associated with AMI (p<0.050). NOS3 T-786C was also related to hypertension (p=0.049). NOS3 intron 4A/B STR was associated with increased concentrations of total cholesterol and apo B. NOS3-786TT/894GT haplotype was associated with increased FMV (p=0.018) than the other haplotypes. CONCLUSIONS: Our data suggest NOS3 and FGB polymorphisms are associated with AMI. NOS3 is also related to hypertension, endothelial dysfunction and variation on serum cholesterol in young adults with AMI.     

Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke

Summary.  Background: Confounding by common causes and reverse causation have been proposed as explanations for the association between high fibrinogen levels and cardiovascular disease. Genetic variants can alter fibrinogen characteristics and are not subject to these problems. Objectives: To determine the fibrinogen plasma levels for genotypic variants in fibrinogen-Aα (FGA Thr312Ala) and fibrinogen-Bβ (FGB − 455G/A), and whether these variants are associated with arterial thrombosis. Methods: Fibrinogen genotypes were determined in a population-based case–control study including women aged 18–50 years; 218 cases with myocardial infarction, 192 cases with ischemic stroke, and 769 healthy controls. Fibrinogen levels were determined in the control population. Results: The FGB − 455G/A variant increased plasma fibrinogen levels, whereas the FGA Thr312Ala variant lowered plasma fibrinogen levels, albeit to a modest extent. The risk of ischemic stroke was altered when the homozygote minor allele was compared with the homozygote major allele. The FGA Thr312Ala single-nucleotide polymorphism (SNP) was associated with a decrease in risk [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.21–0.87], whereas the FGB − 455G/A SNP might have increased the risk (OR 1.76; 95% CI  0.7–4.03). The risk of myocardial infarction was not altered for either SNP (FGA Thr312Ala, OR 0.98, 95% CI  0.40–2.40; FGB − 455G/A, OR 0.98, 95% CI  0.40–2.40). Conclusions: With the genetic variations as markers of plasma fibrinogen levels alterations, thereby ruling out confounding and reverse causation, our results suggest that plasma fibrinogen levels could play a more pronounced role as risk factors for ischemic stroke than for myocardial infarction.     

Elevated plasma fibrinogen γ'' concentration is associated with myocardial infarction: effects of variation in fibrinogen genes and environmental factors

BACKGROUND: Fibrinogen gamma', a fibrinogen gamma-chain variant generated via alternative mRNA processing, has been associated with susceptibility to thrombotic disease. OBJECTIVE: The present case-control study searched for potential determinants of the plasma fibrinogen gamma' concentration and examined the relationship between this variant and risk of myocardial infarction (MI). PATIENTS AND METHODS: The Stockholm Coronary Artery Risk Factor study, comprising 387 postinfarction patients and 387 healthy individuals, was employed. The fibrinogen gamma (FGG) 9340T > C [rs1049636], fibrinogen alpha (FGA) 2224G > A [rs2070011] and fibrinogen beta (FGB) 1038G > A [rs1800791] polymorphisms were determined. The plasma fibrinogen gamma' concentration was measured by enzyme-linked immunosorbent assay. The multifactor dimensionality reduction method was used for interaction analyses on risk of MI. RESULTS: The FGG 9340T > C and FGA 2224G > A polymorphisms, total plasma concentrations of fibrinogen, insulin and high-density lipoprotein, and gender appeared to be independent determinants of plasma fibrinogen gamma' concentration in patients, and the corresponding determinants in controls included FGG 9340T > C and FGA 2224G > A polymorphisms and plasma fibrinogen concentration. An elevated plasma fibrinogen gamma' concentration proved to be an independent predictor of MI [adjusted odds ratio (OR) (95% CI): 1.24 (1.01, 1.52)]. The plasma fibrinogen gamma' concentration was involved in a high-order interaction with total plasma fibrinogen and the FGG 9340T > C and FGA 2224G > A polymorphisms, associated with a further increased risk of MI [OR (95% CI): 3.22 (2.35, 4.39)]. CONCLUSIONS: Plasma fibrinogen gamma' concentration influences the risk of MI, and this relationship seems to be strengthened by the presence of an elevated total plasma fibrinogen concentration and the FGG 9340T and FGA 2224G alleles.     

210名广东籍人β—FBG—455G／A基因多态性分析及与血浆纤维蛋…

OBJECTIVE: To analyze the frequency of beta-fibrinogen (beta-FBG) gene G/A-455 polymorphisms in Guangdong Chinese population and the relationship between genotype and plasma fibrinogen levels. METHODS: DNA of 210 samples were analyzed by using PCR-RFLP. Turbidimetric method for the levels of plasma fibrinogen was performed in 92 samples. RESULTS: The frequency of beta-FBG G/A-455 genotype A/A was 0.038; G/G was 0.514 and G/A was 0.448. The frequency of the A-allele was 0.262. The average plasma fibrinogen level in 46 samples of genotype G/A was (2.18 +/- 0.24) g/L and in 42 samples of G/G genotype was (2.03 +/- 0.25) g/L. There was significant difference between genotype and plasma fibrinogen (P < 0.01). CONCLUSION: The frequency of beta-FBG G/A-455 A-allele in Guangdong Chinese population is higher than that in European. The plasma fibrinogen level in G/A genotype is higher than that in G/G genotype. It suggested that the beta-FBG gene expression might be associated with the genotype.     

儿童单纯性肥胖与纤维蛋白原Bβ-148C/T、Bβ448G/A基因多态性关系的研究

目的 研究纤维蛋白原Bβ-148C/T、Bβ448G/A 基因多态性与儿童单纯性肥胖的相关性,为防治儿童单纯性肥胖提供理论依据.方法 抽取空腹静脉血采用聚合酶链反应限制性酶切方法对纤维蛋白原Bβ-148C/T、Bβ448G/A位点的基因型进行测定.结果 发现Bβ-148C/T基因型的分布在单纯性肥胖组和正常体重组差异有统计学意义(CC 51/67,CT 47/37,TT 8/2,基因型分布P=0.03);儿童单纯性肥胖T等位基因频率明显高于健康对照组(C 149/171,T 63/41,等位基因频率P=0.02),而B13448G/A基因型及等位基因频率的分布在单纯性肥胖组和正常体重组差异无统计学意义(GG 61/69,AG41/32,AA4/5,G 163/70,A49/42,均为P0.05).结论 纤维蛋白原Bβ-148 C/T基因多态性与儿童单纯性肥胖有相关性.而Bβ448G/A基因多态性与儿童单纯性肥胖不相关.     

210名广东籍人β-FBG-455G/A基因多态性分析及与血浆纤维蛋白原水平的关系

目的分析中国广东籍人β纤维蛋白原Ｇ／Ａ４５５（βＦＢＧ４５５Ｇ／Ａ）基因多态性,计算各型的基因频率,测定不同基因型人血浆纤维蛋白原（ＦＢＧ）水平,探讨该基因多态性与基因表达的相关性。方法应用聚合酶链反应限制性酶切分析方法,分析２１０名广东籍人ＤＮＡ样品的βＦＢＧ４５５Ｇ／Ａ多态性,比浊法测定其中９２名血浆ＦＢＧ水平。结果βＦＢＧ４５５Ａ／Ａ纯合子８名,基因型频率为０．０３８;βＦＢＧ４５５Ｇ／Ｇ野生型１０８名,基因型频率为０．５１４;βＦＢＧ４５５Ｇ／Ａ杂合子９４名,基因型频率为０４４８。Ａ等位基因频率为０．２６２。４６名Ｇ／Ａ型血浆ＦＢＧ水平为（２．１８±０．２４）ｇ／Ｌ,４２名Ｇ／Ｇ型为（２．０３±０．２５）ｇ／Ｌ,两组比较差异有显著性（Ｐ＜０．０１）。结论中国广东籍人群中βＦＢＧ４５５Ａ等位基因频率比欧洲一些国家高（Ｐ＜０．０１）。Ｇ／Ａ型血浆ＦＢＧ水平比Ｇ／Ｇ型高（Ｐ＜０．０１）。提示该基因位点多态性与血浆ＦＢＧ的表达有一定相关。