血管紧张素系统基因多态性与阻塞性睡眠呼吸暂停低通气综合征

目的 探讨血管紧张素转换酶(ACE)和血管紧张素原(AGT)基因与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)发病的关系。方法 应用聚合酶链反应(PCR)和限制性长度多态性方法测定无亲缘关系的中国北方汉族男性121例OSAHS患者与100例非OSAHS对照者的ACE和AGT基因多态性的基因型,并检验两组基因型的分布、等位基因频率的差异和基因多态性对OSAHS患者组肥胖表型的效应,分析基因型与睡眠呼吸暂停低通气指数(AHI)、收缩压(SBP)与舒张压(DBP)的关系。结果 ACE基因多态性的基因型分布两组差异无显著性(P>0.05),OSAHS患者组AGT基因多态性的基因型分布和等位基因频率与对照组相比,差异有显著性(P<0.05),OSAHS患者组中AGT基因多态性T等位基因携带者的体重指数(BMI)、颈围(NC)、腰臀比(WHR)明显高于非携带者,AHI、SBP与DBP也相应明显高于非携带者,差异有显著性(P<0.05)。结论 ACE I/D基因多态性可能不参与中国北方汉族男性中心型肥胖及OSAHS的形成。AGT基因多态性可能通过中心型肥胖而导致中国北方汉族男性OSAHS的发生及OSAHS患者高血压的形成。     

血管紧张素原基因启动子区域单核苷酸多态与高血压并发冠心病的关系

目的　研究在中国南方汉人群中 ,血管紧张素原基因 (angiotensinogen ,AGT)启动子区域 2 17位和 2 0位上的二种单核苷酸多态与高血压病 (EH)并发冠心病的关系。方法　运用多重SNaPshot反应 ,对 2 0 5例EH并发冠心病患者、185例EH患者和 185名健康对照者进行G 2 17A和A 2 0C多态基因分型。结果　G 2 17A多态的基因型分布在EH并发冠心病组 (AA =8、AG =71、GG =12 6 )和对照组 (AA =8、AG =37、GG =14 0 )之间有显著性差异 (P =0 0 0 5 ) ;A、G等位基因频率与对照组相比亦有显著性差异 (A 2 1 2 2 %、G 78 78%比A 14 32 %、G 85 6 8% ,P =0 0 12 ) ;A 2 0C多态的基因型分布 (CC、AC、AA)及C、A等位基因频率在二组间的差异无显著性 (分别为CC =5、AC =4 9、AA =15 1比CC =2、AC =6 1、AA =12 2 ,P =0 0 97;C 14 39%、A 85 6 1%比C 17 5 7%、A 82 4 3% ,P=0 2 2 6 )。在男性EH并发冠心病组中 ,G 2 17A和A 2 0C多态的基因型分布及其等位基因频率与对照组相比均有显著性差异 (G 2 17A :AA =7、AG =5 3、GG =86比AA =6、AG =2 8、GG =97,P =0 0 2 2 ;A 2 2 95 %、G 77 0 5 %比A 15 2 7%、G 84 73% ,P =0 0 2 2。A 2 0C :CC =3、CA =2 7、AA =116比CC =2、CA =4 3、AA =86 ,P =0 0 2 3;C 11 30 %     

Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/C for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status.     

血管紧张素原基因M235T多态性与冠状动脉病变的关系

目的研究我国山西及周边地区人群血管紧张素原基因M235T多态性与冠状动脉病变的关系。方法选择152名行冠状动脉造影的住院患者为研究对象,根据冠状动脉病变支数和积分分组,应用聚合酶链反应结合限制片长多态性对患者的基因型和等位基因进行分析并比较。结果冠状动脉病变支数和积分不同者,其TT基因型分布和T等位基因频率不同,该差异有显著性(χ2分别为29.537、28.560、31.970和31.771,均P<0.01)。病变支数和积分与T等位基因频率均呈正相关关系(r分别为0.396和0.395,均P<0.01)。结论血管紧张素原基因变异与冠状动脉病变支数和冠状动脉积分均具有相关性。T等位基因频率越高,冠状动脉病变支数越多,冠状动脉积分越高。     

Association between urinary angiotensinogen levels and renal and cardiovascular prognoses in patients with type 2 diabetes mellitus

Aims/Introduction:  Activation of the renin‐angiotensin system (RAS) in the kidney plays an important role in renal function. The aim of this study was to investigate whether plasma and urinary angiotensinogen levels were associated with renal and cardiovascular prognosis in type 2 diabetic patients.Materials and Methods:  We measured plasma and urinary angiotensinogen levels in the observational follow‐up cohort of 234 Japanese type 2 diabetic patients (144 with normoalbuminuria, 90 with albuminuria) enrolled between 1998 and 1999 and followed them up until the end of 2008. The associations of these markers with the annual decline in the estimated glomerular filtration rate (eGFR) and incidence of renal and cardiovascular composite endpoints (chronic hemodialysis, myocardial infarction, angina pectoris, stroke and cerebral hemorrhage) were evaluated.Results:  At baseline, urinary angiotensinogen levels correlated with urinary albumin‐creatinine ratio, urinary β₂‐microglobulin and inversely with eGFR. In contrast, plasma angiotensinogen levels correlated neither with these renal factors nor with urinary angiotensinogen levels. In the follow‐up study (median duration: 9 years), urinary angiotensinogen, but not plasma angiotensinogen, correlated inversely with the annual change in eGFR (r = −0.51, P < 0.001). When patients were divided into four subgroups according to albuminuria and urinary angiotensinogen levels, patients with albuminuria and high urinary angiotensinogen levels showed a progressive decline of eGFR and a higher incidence of renal and cardiovascular composite endpoints.Conclusions:  These results suggest that the higher level of urinary angiotensinogen in type 2 diabetic patients with albuminuria is a high risk factor for worsening renal and cardiovascular complications. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00172.x, 2011)     

Effects of low protein diet supplemented with ketoacids on local renin - angiotensin system enzyme activities and podocytes loss in patients with diabetic nephropathy

Objective To explore the effects of low-protein diet supplemented with ketoacids on podocytes as well as local RAS in the kidney of patients with diabetic nephropathy. Methods A tal of 61 patients with T2DN and CKD stages 3-4 were included. All the patients were randomly divided into two groups: low protein group (0.6 g•kg BW-1•d-1 and 30 kcal•kg BW-1•d-1, LPD) and LPD +Ketoacids (KA) group (0.6 g•kg BW-1•d-1, 30 kcal kg BW-1•d-1, and Ketoacids 100 mg•kg BW-1• d-1). Blood and 24 h urine samples were collected at baseline and every 3 months for routine examination to evaluate the efficacy of LPD + KA diet. Podocytes loss was evaluated by mRNA expression of nephrin, podocin, and synaptopodin in urine at baseline and every 3 months. Urinary angiotensinogen was detected by ELISA at baseline and every 3 months. Results After 12 months of follow-up, there were no significant difference statistically in declines of GFR between LPD and LPD+ KA group (P＞0.05). Compared with LPD group, proteinuria in LPD+KA group was decreased [(0.43± 0.35) vs (0.15±0.36) g/24 h, P＜0.01]. Patients in two groups were both in good nutritional condition, and KA independently increased the levels of serum albumin and prealbumin (all P＜0.05). The urinary angiotensinogen/creatinine ratio was correlated with GFR (r＝-0.437, P＝0.001), serum creatinine (r＝-0.733, P＝0.000) and proteinuria (r＝-0.851, P＝0.000); while urinary mRNA expression of podocyte markers (podocin and synaptopodin were correlated with proteinuria (r＝0.340, P＝0.012; r＝0.333, P＝0.014; respectively), but had no correlation with GFR and serum creatinine. After 12 months of follow-up, the urinary angiotensinogen/creatinine ratio in LPD+KA group was lower than in LPD group (P＜0.05). The mRNA expression of podocin and synaptopodin were lower in LPD+ KA group compared with LPD group in urinary sediment (P＜0.05). Further correlation analysis suggested that the change of urinary expression of podocin and synaptopodin had a modest but significant correlation with the change urinary angiotensinogen creatinine ratio change (r＝0.305, P＝ 0.026; r＝0.281, P＝0.04, respectively) after treatment for one year. Conclusions Low protein diet supplemented with Ketoacids (LPD + KA) is associated with amelioration of proteinuria, meanwhile nutrition status remains well. The mechanism of these effects may be explained by the role of LPD+KA diet in reducing urine podocyte loss and lowering the angiotensinogen level in the urine.     

中青年脑梗死患者血管紧张素原基因M235T多态性的研究

目的探讨血管紧张素原(AGT)基因M235T多态性与中青年脑梗死(C I)的关系。方法应用聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP)对62例脑梗死患者,58例正常人进行AGT基因M235T多态性分析。结果脑梗死组AGT基因T235等位基因频率为79.84%,235TT基因型频率为64.52%,对照组分别为73.28%和55.17%。两者的差异无统计学意义χ2=1.09,P=0.296;χ2=1.443,P=0.230,235MT、235MM基因型频率两组相比也无差异(P>0.05)。结论AGT基因M235T多态性可能与中国山西汉族中青年人群C I发病无关。     

Plasma interleukin-6 and renin substrate in reactive arthritis,rheumatoid arthritis,and systemic lupus erythematosus

Summary In order to study the role of interleukin-6 (IL-6) in inflammatory disease we monitored plasma levels of IL-6 and acute phase proteins such as C-reactive protein (CRP) and renin substrate (RS) in patients with reactive arthritis (ReA), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Venous plasma samples were collected: (1) during the acute phase or exacerbation of the disease, and (2) several months later during convalescense. Increased mean [95% confidence intervals (CI)] levels of plasma IL-6 were observed in patients with ReA both in the acute phase and later, 229 (177 to 280) ng/l and 197 (134 to 260) ng/l respectively (P <0.001 as compared to controls). The corresponding plasma IL-6 levels in RA patients were 283 (223 to 340) ng/l and 183 (151 to 226) ng/l, respectively (P <0.001 as compared to controls). Plasma IL-6 levels in SLE patients were not increased. Plasma RS levels were increased in all patient groups, but no significant correlation to IL-6 or CRP levels was observed, whereas plasma IL-6 and CRP levels showed a positive correlation in ReA and RA patients.     

血管紧张素原基因多态性与2型糖尿病肾病的相关性研究

目的　探讨血管紧张素原 (angiotensinogen ,AGT)基因多态性与 2型糖尿病肾病的相关性。方法　随机选择 2型糖尿病患者 1 99例 ,分为非糖尿病肾病组 (NDN)和糖尿病肾病组 (DN) ,采用放免分析法检测其 2 4h尿微量白蛋白定量 (2 4hUPro) ,聚合酶链反应 -限制性片段长度多态性 (PCR -RFLP)方法检测其AGT基因多态性 ,分析两者之间的相关性。结果　在所有糖尿病患者中AGT各基因型的Upro水平呈MT >MM >TT ,其中MT与TT相比差异有显著性 ,而AGT基因多态性在NDN组和DN组的分布并无明显差别。结论　AGT基因多态性与 2型糖尿病患者的 2 4hUPro水平有关 ,可能与 2型糖尿病肾病的进程有关。