糖尿病合并冠心病与芳香酯酶基因Q192R多态性分析

目的 :探讨糖尿病 (DM)芳香酯酶 (ArE/PON1)基因Q192R多态性与糖尿病合并冠心病 (DM -CAD)的关系 ,为防治DM -CAD提供理论依据。方法 :调查对象为郑州地区汉族健康人群 6 4例 (对照组 )、2型糖尿病 6 0例 (DM组 )与DM -CAD6 7例 (DM -CAD组 )。测定其血清ArE/PON1活性 ,并用聚合酶链式反应 -单链构型多态性 (PCR -SSCP)分析技术检测ArE/PON1基因Q192R的多态性 ,进行分析研究。结果 :发现对照组、DM组和DM -CAD组均存在ArE/PON1基因 192位点 (Q/R)多态性。对照组基因频率Q为 0 .5 5、R为 0 .4 5 ;DM组为 0 .5 3与 0 .4 7;DM -CAD组为 0 .38与 0 .6 2。DM -CAD组R基因频率明显高于DM组和对照组 (P <0 .0 5 ) ,DM组与对照无显著差异 (P >0 .0 5 ) ,DM与DM -CAD组血清ArE/PON1活性 (分别为 0 .2 2 5± 0 .0 18μ/ml与 0 .2 0 0± 0 .0 19μ/ml)均低于对照组 (0 .2 5 9± 0 .0 18μ/ml) ,DM -CAD组低于DM组 (P <0 .0 5 )。 3组中每组内每种基因型组间酶活性无显著差异。结论 :郑州汉族人群存在ArE/PON1Q192R(GIn/Arg)多态性 ,基因频率分布不同于白种人 ,提示R基因可能是DM合并CAD的危险因素。     

糖尿病肾功能衰竭患者血糖水平与肾功能的关系

在许多国家,糖尿病所致的肾病已成为慢性肾功能衰竭的首位病因［１］,在我国这一趋势也逐渐明显。慢性肾功能衰竭已成为糖尿病的主要致死因素之一。本文通过观察糖尿病肾功能衰竭患者的空腹血糖、尿素氮、肌酐水平的变化,及其相关性,以了解三者的相互关系及其临床意义...     

老年糖尿病并慢性肾功能衰竭患者临终前血糖变化与肾功能关系

对３１例老年糖尿病并慢性肾功能衰竭患者入院后和临终前空腹血糖（ＦＰＧ）、尿素氮（ＢＵＮ）和肌酥（Ｃｒ）间进行对比分析。结果：３者均有极显著性差异（Ｐ＜０．０１）；血糖波动大，不易控制；在ＦＰＧ下降与ＢＵＮ、Ｃｒ升高数值之间呈负相关关系（ｒ＿１＝－０．７１６７，Ｐ＜０．０１；ｒ＿２＝－０．６９３２，Ｐ＜０．０１）。说明热卡量给予不足和应用胰岛素使ＦＰＧ在短期内下降或发生低血糖，均是使病情恶化的因素。     

慢怀肾衰竭血清芳香酯酶活性的变化及临床意义

目的 :研究探讨血清芳香酯酶 ( Ar E)活性在慢性肾衰竭 ( CRF)时的变化规律及其临床意义。方法 :通过测定 5 7例 CRF患者血清 Ar E活性及血脂、脂蛋白、载脂蛋白的浓度 ,然后将患者组和健康对照组进行统计处理 ,对比分析。结果 :CRF患者血清 Ar E活性 ( 0 .2 0 0± 0 .0 4 2 ) U/ ml,Ar E/ TC( 0 .0 4 4± 0 .0 0 3 ) ,Ar E/ HDL- C( 0 .18± 0 .0 4 ) ,Ar E/ HDL3- C( 0 .3 92± 0 .12 0 )水平显著低于对照组。其变化规律与 HDL - C、HDL2 - C、HDL - C/ TC、HDL2 - C/ HDL3- C、Apo- A1 / Apo- B1 0 0 相似 ,且 Ar E的水平与 HDL - C、HDL2 - C、Apo- A1 呈正相关 ,相关系数 r分别为 0 .3 7、0 .5 1和 0 .2 9、Ar E/ TC与 HDL - C/ TC、HDL2 - C/ TC、Apo- A1 / Apo- B1 0 0 的相关系数依次为 0 .60、0 .67、0 .5 7,为正相关关系。血清 Ar E和清蛋白呈正相关 ( r=0 .5 4 3 )而与肌酐呈负相关 ( r=- 0 .3 5 9)。Ar E活性降低先于 TC、HDL - C和 Apo- A1 水平的改变。结论 :血清 Ar E活性是反映 CRF患者并发脂代谢紊乱的较好指标 ,并能提示肾衰竭的严重程度。     

大连地区汉族慢性肾功能衰竭患者的HLA基因多态性

慢性肾功能衰竭是由各种原发的或继发的肾脏疾病所引起的.其发病与HLA基因、种族、地区密切相关[1].我们对312名大连地区、汉族慢性肾功能衰竭患者进行移植术前的HLA基因分型,并与本地区健康对照者[2]进行比较,研究两者间的相关性,现报告如下.     

对氧磷酯酶-1基因多态性与2型糖尿病性肾病的关系研究

目的结合对氧磷酯酶-1(PON1)的活性,探讨其基因多态性与2型糖尿病并发肾病的关系。方法应用聚合酶链反应-限制性片段长度(PCR-RFLP)分析探讨PON1基因A192B多态性在正常对照组、单纯2型糖尿病组和糖尿病肾病组分布情况;血清PON1活性以对氧磷为底物用光电比色法测定。结果①糖尿病肾病组BB基因型和B等位基因频率明显高于糖尿病组(χ2=7.839,P<0.05,χ2=53.22,P<0.01)和正常对照组(χ2=4.237,P<0.05,χ2=29.057,P<0.05)。②92例2型糖尿病患者的PON1活性比81例正常对照组显著降低[(150.9±49.7)kU/L与(226.6±64.9)kU/L,P<0.05],且2型糖尿病并发肾损害者活性下降更显著[(150.9±47.9)kU/L与(103.3±36.8)kU/L,P<0.01],回归分析表明BB基因型是糖尿病肾病的独立危险因素。结论PON1基因多态性与糖尿病性肾病有关。     

血清中芳香酯酶的特性及其与疾病的关系

芳香酯酶主要由肝细胞合成,是依赖Ca~(2+)存在于血浆HDL中的一种酯酶。它能水解氧化型磷脂,抑制氧自由基对HDL和LDL氧化,与脂代谢有密切的关系,因其具有抗动脉粥样硬化的作用而日益受到重视。本文就对芳香酯酶的生物学特点及其与某些疾病的关系进行综述。     

血清中芳香酯酶的特性及其与疾病的关系

芳香酯酶主要由肝细胞合成，是依赖Ca2 存在于血浆HDL中的一种酯酶。它能水解氧化型磷脂，抑制氧自由基对HDL和LDL氧化，与脂代谢有密切的关系，因其具有抗动脉粥样硬化的作用而日益受到重视。本文就对芳香酯酶的生物学特点及其与某些疾病的关系进行综述。     

血清对氧磷酶1活性与2型糖尿病患者颈动脉粥样硬化的关系

目的：探讨血清对氧磷酶1（paraoxonase 1,PON1）活性与2型糖尿病患者颈动脉粥样硬化的关系。方法2型糖尿病患者117例,根据颈动脉彩色多普勒超声测定结果,分为无动脉粥样硬化（AS）组38例,AS组79例;选择同期健康体检者75例（对照组）,测量血压、体质量指数（BMI）、腰臀比、空腹血糖、餐后2小时血糖、糖化血红蛋白、总胆固醇、甘油三酯（TG）、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血尿酸等各项指标,同时测定血清 PON1活性。分析血清PON1活性与颈动脉粥样硬化的关系。结果与对照组比较,糖尿病组血清 PON1（240．0±15．6） kU／L vs （229．5±19．6）kU／L、AS发生率（44．0％ vs 67．5％）、BMI（24．3±3．6）kg／m2 vs （25．8±3．2）kg／m2、腰臀比（0．89±0．05）vs （0．93±0．06）、收缩压（131．0±8．3）mmHg（1 mmHg＝0．133 kPa）vs （134．0±8．8）mmHg、TG （1．8±0．8）mmol／L vs （2．1±1．3）mmol／L等比较差异有统计学意义（P＜0．05）;AS组血清 PON1活性明显低于非AS组（235．5±19．9）kU／L vs （226．7±18．9）kU／L（P＜0．05）;糖尿病患者血清PON1活性与年龄呈负相关（r＝－0．382,P＜0．01）,与血清TG水平呈正相关（r＝0．223,P＜0．05）。结论2型糖尿病患者血清PON1活性显著下降,PON1活性降低与颈动脉粥样硬化发生密切相关。     

Paraoxonase/arylesterase ratio, PON1 192Q/R polymorphism and PON1 status are associated with increased risk of ischemic stroke

Objectives:In recent years, importance of enzyme activity measurements, in addition to genotyping, in epidemiological studies relating paraoxonase 1 (PON1) and vascular disease was emphasized. This is the first report evaluating paraoxonase and arylesterase activities as risk factors for ischemic stroke. In addition, PON1 192Gln(Q)/Arg(R) and 55Leu(L)/Met(M) polymorphisms were also analyzed.Design and methods:The study population was comprised of 108 ischemic stroke patients and 78 controls. Enzyme activities were determined by spectrophotometric assays and for genotyping, standard PCR protocols followed by restriction enzyme digestions were used.Results:The prevalence of the PON1 192RR genotype was increased among stroke patients (16.7%) as compared to controls (9.0%, P = 0.129). Paraoxonase and arylesterase activities and PON1 activity ratio (paraoxonase/arylesterase) were found to be lower in patients than in controls. Logistic regression analysis revealed PON1 activity ratio (odds ratio, OR = 0.697, 95% CI, 0.541 to 0.898, P = 0.005), PON1 192RR genotype (OR = 3.434, 95% CI, 1.159 to 10.178, P = 0.026) and PON1 status (PON1 activity ratio combined with PON1 192RR genotype; OR = 1.406, 95% CI, 1.038 to 1.905, P = 0.028) as significant predictors of stroke.Conclusions:This study identified PON1 activity ratio, PON1 192RR genotype and PON1 status as important risk factors for ischemic stroke.     

Ⅰ型对氧磷酯酶基因Gln/Arg192遗传多态性与冠心病相关性的初步研究

目的 探讨中国北方地区I型对氧磷酯酶(paraoxonase l，PON1)基因Gln／Arg192遗传多态性与冠心病发病的关系。方法 应用聚合酶铁反应(polymerase chain reaction，PCR)及限制片段长度多态性(restriction fragment length polymorphisms，RFLP)技术，检测49例老年冠心病患者和38例健康老年对照者的PONl—Gln／Arg192基因多态性，等位基因以A／B表示。结果 冠心病组与健康组比较各基因型分布差异具有显著性意义(χ^2＝6．35，P＝0.042)。B等位基因在冠心病组明显增高(0．56vs0．37)。B等位基因是中国北方地区冠心病发病的危险因素(OR＝2.19，95％CI：1．19～4.05)。结论 PONl基因Gln／Arg192遗传多态性与中国北方地区冠心病发病明显相关。该酶切位点多态性具有明显的种族差异。     

汉族人胆固醇酯转运蛋白Taq Ⅰ B基因多态性与2型糖尿病的关系

目的分析胆固醇酯转运蛋白(CETP)血浆水平及其TaqⅠB基因多态性与2型糖尿病(T2DM)的关系。方法采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测103例健康对照组、102例T2DM患者CETP第一内含子TaqⅠB多态性基因型,ELISA方法检测血浆CETP浓度,探讨了其对血脂、脂蛋白和apo水平的影响。结果T2DM组血浆CETP水平明显高于对照组;两组CETPTaqⅠB多态性基因型和等位基因频率分布差异无显著性意义,与性别、家族史、吸烟史及体质指数(BMI)无明显相关性。对照组CETPTaqⅠB等位基因型与血脂水平之间无明显关联性,但T2DM组不同基因型间HDL-C与apoAⅠ水平差异有统计学意义,B1等位基因频率与低HDL-C血症密切相关。结论CETP水平、CETPTaqⅠB基因多态性与T2DM脂代谢存在一定的相关性,可能是糖尿病脂代谢异常的重要遗传因素。     

2型对氧磷脂酶基因311 Cys/Ser多态性与糖尿病肾病的相关性研究

目的 探讨2型对氧磷脂酶(PON2)基因311Cys／Ser多态性与2型糖尿病肾病的相关性及其与血脂的关系。方法 采用聚合酶链式反应-长度片段多态性(PCR-RFLP)技术，对78例2型糖尿病患者(其中26例单纯性2型糖尿病，52例糖尿病肾病)和30例健康对照者，PCIN2基因311Cys／Ser多态性进行检测。结果 PON2基因311Cys／Ser多态性的基因型频率和等位基因频率在2型糖尿病合并大量蛋白尿组与对照组间差异有统计学意义，Ser等位基因在2型糖尿病合并大量蛋白尿组明显增高。结论 PON2基因311Cys／Ser遗传多态性与中国甘肃地区2型糖尿病并发肾病的发病具有相关性。     

PC-1基因K121Q变异与2型糖尿病肾病的关系

目的探讨浆细胞膜糖蛋白(PC-1)基因第4外显子K121Q多态性与2型糖尿病肾病的相关性。方法应用多聚酶链反应(PCR)结合限制性酶切技术检测青岛地区50例2型糖尿病患者和48例正常人PC-1基因K121Q的多态性分布情况。结果正常对照组中KK基因型38例(79.2%),KQ基因型10例(20.8%),QQ基因型0例(0.00%),K、Q等位基因频率分别为89.6%和10.4%。糖尿病患者中KK基因型41例(82%),KQ基因型9例(18%),QQ基因型0例(0.00%),K、Q等位基因频率分别为91%和9%,2组人群的基因型和等位基因频率无显著性差异(P>0.05)。结论PC-1基因多态性与2型糖尿病及2型糖尿病肾病无明显相关性,QQ基因型不是2型糖尿病及2型糖尿病肾病发病的危险因子。     

Frequency of angiotensin-converting enzyme gene polymorphism in Turkish type 2 diabetic patients

We aimed to investigate the angiotensin-converting enzyme (ACE) gene polymorphism, ACE activity and their associations with diabetic complications in Turkish patients with type 2 diabetes mellitus. A total of 143 patients and 133 controls were screened for ACE gene I/D polymorphism by using polymerase chain reaction. Serum ACE activities were determined spectrophotometrically. There was no significant difference in the distribution of ACE I/D genotypes between patients and controls. The patients with DD genotype had a higher ACE activity than those with ID and II. Hypertensive diabetic patients with DD genotype had higher ACE activities than those with ID and II. There was no significant difference in the distribution of ACE I/D genotypes between patients with and without nephropathy, retinopathy and hypertension except for patients with and without neuropathy. In patients with DD genotype, creatinine clearance correlated with duration of diabetes. The grade of retinopathy was correlated with duration of diabetes in DD and ID genotypes. The highest ACE activity was measured in hypertensive diabetics with DD genotype. ID genotype was suggested to be a risk factor and II was suggested to be protective for diabetic neuropathy. The DD and ID genotypes might be a predictor for the development of retinopathy in relation to duration of diabetes.     

雌激素受体基因多态性与2型糖尿病患者骨密度的关系

目的探讨雌激素受体(ER)基因多态性与2型糖尿病患者骨密度(BMD)的相关性。方法运用双能量X线吸收法(DEXA)测定61例2型糖尿病患者的BMD,PCR-RFLP检测ER基因多态性。结果2型糖尿病组PP型的BMD与Pp型相比,在L2,L3,L4及L2～4有显著的统计学差异(P值分别为0.045,0.021,0.019和0.019);与pp型相比,在L4有显著的统计学差异(P=0.037)。Pp型与pp型相比,各部位BMD均无显著的统计学差异。ER基因型分布频率为PP型0.128,pp型0.333,Pp型0.539,PP型腰椎BMD明显低于Pp型与pp型。结论2型糖尿病易合并骨量减少和骨质疏松,ER基因PP型与2型糖尿病患者腰椎低BMD密切相关。     

Angiotensin-converting enzyme gene polymorphism and stroke in type 2 diabetic patients in Taiwan

BACKGROUND: The effect of traditional risk factors on the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and stroke was rarely studied previously. We investigated such effect in Taiwanese type 2 diabetic patients. MATERIALS AND METHODS: A total of 872 (422 men and 450 women) patients aged 63.5 (SD: 11.6) years were recruited. Among them, 92 cases (48 men and 44 women) had stroke. Polymerase chain reaction was used to classify the genotypes as II, ID and DD. Analyses were performed in separate sexes. RESULTS: The adjusted odds ratios for stroke for ID vs. II and DD vs. II were 0.837 (0.413-1.697) and 1.778 (0.596-5.300), respectively, for men; but were 1.700 (0.824-3.505) and 3.706 (1.375-9.985), respectively, for women. In models assuming recessive (DD vs. II + ID), dominant (DD + ID vs. II) and additive (II = 0, ID = 1 and DD = 2) transmission, none of the odds ratios was significant for men; but were all significant for women: 2.784 (1.137-6.818), 1.996 (1.006-3.962) and 1.877 (1.155-3.050), respectively. In models using patients without risk factors (hypertension, obesity, smoking or dyslipidaemia ) as a referent group and comparing them to patients with the risk factor and with ID/II, and with DD genotypes, all models (except for smoking) favoured an increasing trend of risk with patients having the risk factor and DD genotype at the highest risk in women. Similar trends for hypertension and dyslipidaemia were also observed in men. CONCLUSION: Traditional risk factors play an important role in the association between the ACE genotypes and stroke. Patients with DD genotype and having traditional risk factors are at the highest risk.