血管紧张素Ⅰ转换酶基因多态性与2型糖尿病肾病的关系

研究血管紧张素Ⅰ转换酶基因多态性是否与２型糖尿病肾病相关。方法用聚合酶链反应扩增ＡＣＥ基因第１６内含子的一个２８７ｂｐ的插入／缺失基因片段，１．５％琼脂糖凝胶电泳，紫外线灯下观察结果。结果各组间ＡＣＥ Ｉ／Ｄ基因型和等位基因频率分布无明显差异。     

2型糖尿病肾病与中心性肥胖的相关研究

目的研究2型糖尿病肾病（DN）与中心性肥胖之间的关系。方法应用Logistic回归分析方法回顾性分析352例2型糖尿病患者的年龄、病程、血压、体重指数、腰臀比、空腹血糖、糖化血红蛋白、血脂等与糖尿病肾病间的相关性。结果糖尿病肾病（DN）组的病程、体重指数、腰臀比、三酰甘油、胆固醇、低密度脂蛋白、尿素氮、肌酐均明显高于糖尿病非肾病（DM）组;Logistic回归分析提示DN与病程、腰臀比、三酰甘油、胆固醇、低密度脂蛋白有相关性。结论减轻体质量,控制血脂、血压、血糖可在某种程度上延缓DN的发生与发展。     

Lack of association between arylamine N-acetyltransferase 2 (NAT2) polymorphism and systemic sclerosis

Objectives It has been shown that exposure to some environmental toxins may induce scleroderma-like illness in predisposed individuals, but the etiopathogenesis of the idiopathic form of systemic sclerosis (SSc) remains obscure. The genetic background of this illness has been confirmed in multiple studies. We investigated whether patients with SSc differ from healthy subjects with regard to the enzymatic activity of polymorphic N-acetyltransferase 2 (NAT2).Methods The study was carried out in 39 patients with SSc; 15 fulfilled the criteria of diffuse SSc (dSSc) and 24 of limited SSc (lSSc); an ethnically matched control group consisted of 100 healthy volunteers. Acetylation phenotype was estimated using the isoniazid as a model drug. The most common mutations in the Caucasian population at positions 481T, 803G, 590A and 857A on the NAT2 gene were determined using the polymerase chain reaction–restriction fragment length polymorphism method with deoxyribonucleic acid (DNA) extracted from peripheral blood.Results In the group of patients with SSc, the frequency of fast acetylator genotypes was 38.5% (95% CI 23.4–55.4), while that for the genotypes coding slow acetylator status was 51.3% (95% CI 34.8–67.6).There was a strong correlation between NAT2 phenotype and NAT2 genotype with a concordance of 97%. We did not observe a preponderance of slow acetylators among patients with SSc and in two subsets of SSc. With the sample size analyzed in the present study, there is a 90% probability of detecting significant differences in distribution of slow, fast, and intermediate phenotypes between patients with SSc and controls, there is a difference of at least 30.3, 28.7 and 21.9% in the distribution of these phenotypes in the general population, respectively.Conclusion Acetylator status does not seem to be the significant factor in the development of SSc in patients with both subsets of this autoimmune disease, but further studies are required to confirm this conclusion.     

RANTES基因多态与2型糖尿病肾病的临床研究

目的探讨RANTES基因启动子G-403A多态与2型糖尿病肾病之间的关系。方法用聚合酶链反应限制性片段长度多态性技术（PCR-RFLP）检测252例RANTES基因启动子G-403A多态的基因型,其中2型糖尿病患者170例（糖尿病非肾病组76例,糖尿病肾病组94例）;正常对照组82例,并对各组间的等位基因频率与基因型频率进行比较。结果糖尿病肾病组的AA基因型频率（24．5％）明显高于正常对照组（14．6％）。糖尿病肾病组的A等位基因频率（52．1％）明显高于正常对照组（40．3％）,差异具有统计学意义（P〈0．05）。结论RANTESG-403A多态与糖尿病肾病的发生有相关性。     

Lack of association between arylamine N-acetyltransferase 2 (NAT2) polymorphism and systemic lupus erythematosus

The slow arylamine -acetyltransferase 2 (NAT2) phenotype frequently has been assumed to be associated with an elevated risk to develop a lupus-like syndrome after administration of drugs such as procainamide or hydralazine. Moreover, there are conflicting data on the role of acetylator phenotype as a susceptibility factor for systemic lupus erythematosus (SLE). Because most investigations have previously been conducted with relatively small sample sizes, the present study was performed to clarify the possible association between genotypes and SLE among a large European cohort. In a case-control study, 209 patients with SLE (194 women, 15 men) were enrolled and matched by gender to 209 controls without clinical signs of inflammatory diseases. All SLE patients fulfilled at least four of the revised American College of Rheumatology classification criteria of SLE. was genotyped for seven known mutations by polymerase chain reaction/restriction fragment length polymorphism. The frequency of slow acetylation genotypes in SLE patients (59.8%) did not differ significantly from controls (56.5%). The adjusted odds ratio (OR) was 0.95 (95% confidence interval, 0.59-1.53). Further differentiation to gender, cigarette consumption, allergic disorders and specific SLE manifestations revealed an equal distribution of genotypes in all subgroups. We conclude that this large genotyping study in a Caucasian population demonstrated a lack of evidence for an association of the slow acetylator genotype with SLE.     

对氧磷脂酶2及载脂蛋白E基因多态性与2型糖尿病肾病相关分析

目的探讨对氧磷脂酶2（PON2）基因S311C及载脂蛋白（ApoE）基因变异单独及联合作用对2型糖尿病肾病的影响。方法应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）检测福建地区210例2型糖尿病（T2DM）患者（113例糖尿病肾病患者，97例糖尿病非肾病患者）和105例健康对照者的PON2基因S311C及ApoE基因多态性。结果①糖尿病肾病组PON2CC基因型及C等位基因和ApoEε3／4＋ε4／4基因型及84等位基因频率明显高于糖尿病非肾病组及正常对照组（P〈0．05）；②SC＋CC与ε3／4＋ε4／4基因型并存时对糖尿病肾病的发生具有协同效应（x^2=20．89，P=0．00）；③T2DM患者中CC及ε3／4＋ε4／4基因型有较高的总胆固醇、低密度脂蛋白水平（P〈0．05）；④Logisitic回归分析表明：CC及ε3／4＋ε4／4基因型是糖尿病肾病发生的独立变异危险因素（P〈0．05）。结论PON2、ApoE基因多态性可通过血脂代谢紊乱而影响2型糖尿病肾病的发生。     

血管紧张素转换酶基因多态性与老年人动态血压相关性探讨

目的　探讨老年人血压与血管紧张素转换酶 (ACE)基因多态性的相关性。方法　运用聚合酶链反应 (PCR)技术检测 10 6例老年高血压病人 (高血压组 )的ACE基因多态性 ,根据PCR检测结果 ,分为DD基因型 (n =2 4)、II基因型 (n =40 )及ID基因型 (n =42 )三个亚组 ,分别进行偶测血压 (CBP)及动态血压 (ABP)检测 ,观察三种基因型之间的血压差异 ,另设同期体检的 5 1例老年人作为对照组。结果　CBP参数在三个亚组间差异无显著性 ,ABP参数中 ,DD型亚组的 2 4h平均收缩压和平均动脉压较II型亚组显著增高 ,P <0 .0 5。结论　ACE基因的插入 缺失多态性对老年高血压有影响 ,ABP较CBP敏感     

N-acetyltransferase-2 polymorphism, smoking and type 1 diabetic nephropathy

The N-acetyltransferase (NAT2) polymorphism has been suggested to be related to diabetic microvascular complications. To study the distribution of NAT2 genotypes in Caucasian type 1 diabetic patients with and without diabetic nephropathy, 214 adult type 1 diabetic patients and 53 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In addition, 75 young type 1 diabetic patients were genotyped, and 70 of them also phenotyped by caffeine. Of the adult patients, 83 had normal albumin excretion, 58 had microalbuminuria, and 73 had overt diabetic nephropathy. NAT2 allele frequencies were similarly distributed between the diabetic patients and healthy individuals: 0.29/0.2 5 (NAT2*4), 0.03/0.04 (NAT2*7B), 0.25/0.27 (NAT2*6A), and 0.43/0.44 (NAT2*5B), and within the diabetic subgroups. Because smoking is a known risk factor for diabetic nephropathy, nonsmoking and smoking patients were analysed separately. NAT2 allele frequencies differed significantly between the nonsmoking normoalbuminuric, microalbuminuric and nephropathic patients: 0.18/0.41/0.30 (NAT2*4), 0.04/0.00/0.02 (NAT2*7B), 0.35/0.18/0.17 (NAT2*6A), 0.43/0.41/0.50 (NAT2*5B), P = 0.013. In nonsmoking fast acetylators odds ratio for microalbuminuria and nephropathy was 3.1 (95% confidence interval 1.36-7.05), P = 0.007 by logistic regression. In smokers, a nonsignificant odds ratio was found [0.31 (95% confidence interval 0.08-1.2), P = 0.09]. Smoking is a strong confounding factor in relation to NAT2 analyses and diabetic nephropathy. According to our data, in nonsmoking type 1 diabetic patients fast NAT2 genotype implies an increased risk for diabetic nephropathy.     

2型糖尿病高血尿酸与糖尿病肾病的相关性研究

目的评估2型糖尿病患者血尿酸、肾小球滤过率及尿蛋白排泄率水平,探讨2型糖尿病的高血尿酸水平与糖尿病肾病的关系。方法根据血尿酸浓度将503例2型糖尿病患者分为高尿酸组和正常尿酸组,分别检测两组血压、人体测量学指标、糖化血红蛋白、血脂、血尿酸、血肌酐及尿蛋白排泄率等指标,计算肾小球滤过率,比较两组患者一般临床资料、肾小球滤过率及尿蛋白排泄率水平。结果高尿酸组中的无蛋白尿患者、微量白蛋白尿患者、大量白蛋白尿患者的肾小球滤过率均较正常组降低(P<0.05),差异有统计学意义。高尿酸组中大量蛋白尿的患病率明显高于正常组(P<0.05),而两组间微量蛋白尿的患病率比较差异无统计学意义。结论 2型糖尿病患者高血尿酸与糖尿病肾病相关,血尿酸可更直观地预测肾小球滤过率下降水平。     

血管紧张素转化酶基因多态性与Ⅱ型糖尿病肾病

目的探讨血管紧张素转化酶(ACE)基因插入/缺失多态性与Ⅱ型糖尿病(NIDDM)肾病的关系。方法聚合酶链反应。结果无肾病的NIDDM患者中 ,ACE基因型频率与正常人比较 ,I/I基因型和I/D D/D基因型频率分布差异有显著性意义(P<0.05) ;有肾病的NIDDM患者中 ,ACE基因型频率与正常人比较 ,D/D基因型和I/D I/I基因型频率分布差异有显著性意义(P<0.05)。结论I/I基因型是NIDDM肾病患者的保护性基因 ;而D/D基因型是NIDDM肾病患者的易感基因     

ACE基因多态性与2型糖尿病肾病的相关性研究

目的 探讨血管紧张素Ⅰ转换酶(ACE)基因的插入／缺失多态性与2型糖尿病(type 2 diabetes mellitus，T2DM)患合并肾病的关系。方法采用聚合酶链反应技术检测109例T2DM患(其中合并肾病患37例，未发生肾病患72例)和260例健康对照组ACE基因插入／缺失多态性。结果糖尿病肾病患的DD基因型频率和D等位基因频率有高于无肾病糖尿病患组的趋势，其频率差异接近显性水准(75．7％vs55．6％，P=0．070；87．8％vs77．1％，P=0．057)。DD基因型糖尿病患合并肾病的频率高于其他基因型，差异有统计学意义(41．2％vs22．0％，P=0．040)。对糖尿病病程与ACE基因多态性的交互作用分析发现，DD基因型与5年以上病程存在交互作用(OR=3．75，95％CI；1．019～13．795)。结论ACE基因的DD基因型可增高T2DM患并发肾病的危险性，并且与糖尿病病程有交互作用。     

AT1R、ACE基因多态性与东乡族原发性高血压的关系及其对降压药疗效的影响

目的：探讨血管紧张素转换酶（ACE）、血管紧张素Ⅱ（AngⅡ）Ⅰ型受体（ATIR）基因多态性与甘肃东乡族原发性高血压（EH）的关系。对不同基因型患者使用AT1R拮抗剂治疗，观察其疗效。方法：应用聚和酶链反应（PCR）方法检测汉族健康131例、东乡族健康102例、汉族EH198例、东乡族EH115例的AT1RA／C、ACE I／D基因多态性。随机选取60名EH患者，按其基因型分成AA和AC（AA、AC为基因型）两组，使用缬沙坦治疗8周，比较治疗前后血压变化。结果：ACE基因Ⅱ型在汉族EH组明显高于东乡族EH组（P〈0．05），ID基因型在东乡族EH组明显高于汉族EH组（P〈0．01）；AT1R基因AC型汉族EH组明显高于东乡族EH组（P〈0．05）；AA型在东乡族EH组明显高于汉族EH组（P〈0．05）。使用缬沙坦治疗8周，各基因型在治疗后患者血压均下降显著（P〈0．05）。不同基因型之间治疗后比较，降压效果无差异。结论：AT1R基因AA型和ACE基因ID型与东乡族EH有关；ACE基因Ⅱ型和AT1R基因AC型与汉族EH有关，C和D等位基因与汉族和东乡族EH无关。使用缬沙坦对不同基因型患者进行药物治疗，降压疗效相同，说明降压疗效与基因型无关。     

血管紧张素转换酶基因多态性与原发性高血压血栓前状态的关系

目的　探讨血管紧张素转换酶 (ACE)基因I/D多态性与原发性高血压 (EH)及高血压血栓前状态 (PTS)的关系。方法　PCR检测 6 1例原发性高血压病人和正常对照组 2 8例的ACE基因I/D多态性 ;发色底物法测t PA、PAI 1活性 ,酶联免疫吸附双抗夹心法 (ELISA)测vWF含量。结果　高血压组DD基因型频率显著高于对照组 (P <0 0 5 ) ,但D等位基因频率分布在高血压组和正常组之间差异无显著意义 (P >0 0 5 )。高血压组t PA活性降低 ,PAI 1活性、vWF含量升高 (P均 <0 0 0 1)。高血压组DD型t P活性明显低于ID、II型 (P <0 0 0 1) ,而ID、II型之间差异无显著意义 (P >0 0 5 ) ,DD型PAI 1活性明显高于ID、II型(P <0 0 0 1) ,而ID、II型之间差异无显著意义 (P >0 0 5 ) ,vWF在DD、ID、II型三者之间差异无显著意义 (P>0 0 5 )。结论　DD型是原发性高血压发病的危险因素。原发性高血压存在血栓前状态。t PA、PAI 1的变化与血管紧张素转换酶基因I/D多态性有关 ,DD基因型可引起血栓前状态。     

D-二聚体、纤维蛋白原及胱抑素C与2型糖尿病肾病的关系

目的：探讨D-二聚体（ DD）、纤维蛋白原（ Fib）及胱抑素C（ CysC）水平与2型糖尿病肾病的关系。方法选择2012年1月-2013年12月在该院内分泌科住院的2型糖尿病患者185例,健康体检者47例为对照组（ NC组）。测定其空腹DD、Fib、CysC水平,并按照24 h尿白蛋白排泄率（ UAER）将糖尿病患者分为：正常蛋白尿组（ NA组,UAER＜30 mg· d-1）108例、微量蛋白尿组（MA组,UAER 30～300 mg· d-1）51例、临床蛋白尿组（CP组,UAER ＞300 mg· d-1）26例。观察DD、Fib、CysC与糖尿病肾病之间的关系。结果 MA组和CP组DD、FIB、CysC水平均显著高于NC组及NA组,差异具有统计学意义（均P＜0．05）,CP组与MA组相比亦明显升高（均P＜0．05）;MA组和CP组DD、CysC阳性率显著高于NA组（均P＜0．05）。直线相关分析显示DD、FIB和CysC与UAER均呈正相关（r分别为0．380,0．480,0．819,P均＜0．05）结论2型糖尿病患者处于血栓前状态和继发性纤溶亢进,糖尿病肾病患者尤为明显;DD、FIB和CysC水平与糖尿病肾病的发生、发展密切相关。     

Angiotensin-converting enzyme inhibitors and type 2 diabetic nephropathy: a meta-analysis

OBJECTIVE: To perform a meta-analysis on studies evaluating the effect of angiotensin-converting enzyme (ACE) inhibitors on diabetic nephropathy in patients with type 2 diabetes mellitus. METHODS: A computerized literature search was conducted for articles of studies comparing ACE inhibitors with a control in patients with diabetes, in which measurement of albuminuria or proteinuria was an outcome. Each article was abstracted by two of the authors. Data from the articles were presented as geometric or arithmetic means. The data were summarized separately by using standard techniques for meta-analysis. MAIN RESULTS: Statistically significant reductions in albuminuria were observed regardless of whether data were described with geometric or arithmetic means. Both were associated with significant heterogeneity. When studies reporting geometric means were stratified and analyzed, the heterogeneity was lost and statistically significant reductions in albuminuria were observed. The same procedure was repeated for studies reporting arithmetic means, but heterogeneity remained. CONCLUSION: The ACE inhibitors produce statistically significant reductions in albuminuria associated with significant heterogeneity of effect. Stratification reduces the heterogeneity and supports treatment with ACE inhibitors to reduce the progression of nephropathy in patients with type 2 diabetes mellitus.     

MMP-9 -1562C/T基因多态性与2型糖尿病肾病的关系研究

摘要 目的：探讨2型糖尿病（T2DM）患者基质金属蛋白酶-9基因-1562C/T（MMP-9 -1562C/T）多态性与糖尿病肾病（DN）的关系以及与DN不同病期的相关性。方法：将150例T2DM患者按DN诊断标准分为DN组与非肾病（NDN）组,DN组分为微量白蛋白尿期、临床白蛋白尿期和肾功能不全期。另择52例健康人作为正常对照（NC）组。应用限制性片段长度多态性分析各组基因型。结果：DN组的HbA1c、SBP、Cr、BUN、UAER值高于NDN、NC组（P<0.01）。DN组分别和NDN组、NC组之间基因型分布差别均有统计学意义（P<0.01）。T2DM中CC、CT、TT各基因型DN发病率递减,分别为59.7%、56.7%、34.9%。C和T等位基因DN发病率分别为59.2%、40.5%,携T等位基因者发生DN的风险是携C等位基因者的0.47倍（P<0.01,95%CI 0.29～0.75）;DN组内3期TT基因型与T等位基因频率随肾功能降低而递减;结论：MMP-9 -1562C/T基因多态性与DN发生有关,T等位基因是DN患者的保护基因。     

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with allergic contact dermatitis

Angiotensin-converting enzyme (ACE) plays an important role in the physiological control of blood pressure and inflammation. Insertion/deletion (I/D) polymorphism of the gene for ACE was investigated in relation to cardiovascular, cerebrovascular, neurodegenerative and inflammatory diseases. The purpose of the present study was to investigate the possible association between allergic contact dermatitis and insertion/deletion polymorphism of the ACE gene. A total of 90 patients with allergic contact dermatitis and 160 control persons were enrolled in the present study. ACE I/D genotypes were determined by the polymerase chain reaction. Allelic frequencies and genotype distribution of the ACE I/D polymorphism in the patient group were significantly different from control group (ACE II genotype 30.0% versus 17.5%, P = 0.022; ACE I allele 51.7% versus 39.4%, P = 0.008). Our data suggest that the ACE polymorphism could be a risk factor for patients with allergic contact dermatitis.     

Kinins are involved in the antiproteinuric effect of angiotensin-converting enzyme inhibition in experimental diabetic nephropathy

The present study examined non-insulin-treated streptozotocin (STZ)-induced diabetic rats to determine the role of kinins in diabetic nephropathy. Their involvement in the renoprotective effect of the angiotensin-converting enzyme inhibitor (ACEI) ramipril was investigated using the bradykinin (BK) B(2)-receptor antagonist, icatibant (HOE 140), or a combination of the two drugs.Although, none of the treatments prevented the decline of the glomerular filtration rate (GFR) in diabetic rats, ramipril (3 mg/kg/day), but not icatibant (HOE 140; 500 microg/kg/day), prevented proteinuria in these animals. However, the antiproteinuric effect of ramipril was reduced by 45% when combined with icatibant. To explore whether the renal kallikrein-kinin system (KKS) belongs to the underlying mechanisms of these findings, we also determined urinary BK levels, renal kallikrein (KLK) and angiotensin-converting enzyme (ACE) activity as well as renal cortical mRNA levels of neutral endopeptidase 24.11 (NEP) and low-molecular weight (LMW) kininogen. STZ led to a reduction of renal KLK and ACE activity and NEP expression and to a three-fold increase of urinary BK excretion and renal kininogen expression. Icatibant given alone had no effect on these parameters. In contrast, ramipril treatment normalized urinary protein and BK excretion as well as kininogen mRNA expression without affecting NEP mRNA expression or KLK and ACE activity.Our data demonstrate that renal BK is increased in severe STZ-induced diabetes mellitus, but may affect glomerular regulation only to a minor degree under this condition. However, kinins are partly involved in the antiproteinuric action of ACEI at this stage of diabetic nephropathy.     

血管紧张素转换酶基因多态性与小儿过敏性紫癜及紫癜性肾炎的关联性

目的：探讨血管紧张素转换酶（ACE）基因多态性与小儿过敏性紫癜（HSP）及紫癜性肾炎（HSPN）的相关性。方法：选择106例HsP患儿,其中HSPN患儿32例,在HSPN中单纯性血尿13例,蛋白尿19例,肾功能不全12例,肾脏活检依据ISKDC病理分级,其中Ⅰ～Ⅱ级11例,Ⅲ～Ⅵ级17例。正常对照儿童100例。通过聚合酶链反应（PCR）检测ACE基因多态性并鉴定其基因型。结果：@HSP患儿与正常对照组间ACE基因型分布差异无统计学意义p0．05）,但在HSPN组中,DD基因型及D等位基因频率则明显高于正常对照组（P〈0．0167）;②在HSPN中,DD基因型在表现有大量蛋白尿（尿蛋白〉50mg／24h）、明显血尿（镜检RBC〉3＋／HP）及非轻度肾脏病理损害（Ⅲ～Ⅵ级）组中的频率明显高于对照组（P〈0．05）,但在肾功能正常组（尿肌酐〈1．5mg／d1）和肾功能不全组（尿肌酐〉1．5mg／d1）中,ACE基因型分布则差异无统计学意义（P〈0．05）。结论：ACE基因多态性可能与HSP的发病及其HSPN肾功能的改变无关,但可能与HSPN的发病、血尿、蛋白尿及肾脏病理损害的严重程度有关。     

骨桥蛋白基因单核苷酸多态性与2型糖尿病合并糖尿病肾病的关联研究

目的 探讨骨桥蛋白基因rs11730582、rs11439060和rs28357094多态性与糖尿病肾病的关系.方法 以2015年7月-2016年3月于长江大学附属第一医院内分泌科住院的湖北地区汉族2型糖尿病病人600例为研究对象.应用质谱法研究骨桥蛋白基因rs11730582、rs11439060和rs28357094多态性在2型糖尿病肾病组(334例,病例组)和2型糖尿病非肾病组(266例,对照组)中的基因频率分布.结果 位点rs28357094在病例组和对照组中均表现为纯合子TT,不具有多态性.位点rs11730582和rs11439060的等位基因频率和基因型频率的比较差异无统计学意义.连锁不平衡分析显示rs11730582和rs11439060之间有较强的连锁不平衡,单体型分析发现T-G、C-delG、T-delG 3种单体型,这些单体型的差异比较也无统计学意义.结论 骨桥蛋白基因rs11730582、rs11439060和rs28357094多态性与湖北地区汉族居民2型糖尿病合并肾病无关.