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1.
Single-nucleotide polymorphisms in genes related to oxidative stress are a risk factor for the development of diabetes and its complications. The allele and genotype frequencies of missense polymorphism Ala-9Val and Val16Ala in Mn-SOD and Arg213Gly in EC-SOD genes were studied in (a) patients with Type 2 diabetes mellitus (T2DM) without any complication (T2DM), (b) diabetic nephropathy (DN), (c) non-diabetic nephropathy (NDN) and (d) control healthy subjects from Western region of India. The PCR products were digested with BshTI, BsaWI and Eco52I restriction enzymes to detect Ala-9Val, Val16Ala and Arg213Gly polymorphisms respectively. The frequency of Val allele of Ala-9Val (P?=?0.568 and P?=?0.571) and Ala allele of Val16Ala (P?=?0.993 and P?=?0.152) polymorphisms of Mn-SOD gene did not show a significant difference in patient with T2DM and NDN compared to control subjects respectively. Frequency of Val allele of Ala-9Val (42.8 % vs. 61.5 %, P?<?0.001) and Ala allele of Val16Ala (39.0 % vs. 53.5 %, P?=?0.005) polymorphisms of Mn-SOD gene was significantly higher in patients with DN than that of patient with T2DM. For Arg213Gly polymorphism of EC-SOD gene, the Gly allele frequency in T2DM and NDN group did not significantly (P?=?0.993 and P?=?0.152 respectively) differ from control subjects as well as non-significantly higher in DN compared to T2DM. These results suggests that Ala-9Val and Val16Ala polymorphism in Mn-SOD is not involved in development of diabetes but may play a crucial role in determining genetic susceptibility to diabetic nephropathy in Western Indian Type 2 diabetic patients. Our data found a lack of association of EC-SOD (Arg213Gly) polymorphism with development of diabetes and diabetic nephropathy.  相似文献   

2.
ACE基因多态性与胰岛素依赖性糖尿病伴肾病的关系探讨   总被引:3,自引:1,他引:3  
目的:研究ACE基因与IDDM肾病关系。方法:用扩增片段长度多态性方法,分析68例IDDM患者(其中24例为IDDM伴肾病者,44例为IDDM不伴肾病者)和57例正常人的ACE基因插入(I)/缺失(D)多态性。结果:IDDM患者和正常人之间ACE基因I/D多态性频率差异不显著,IDDM伴肾病组D等位基因频率明显高于IDDM不伴肾病组(P〈0.05),DD基因型也有相同趋势(0.05〈P〈0.1)。  相似文献   

3.
Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes in 261 Iranian casecontrol pairs. Methods: 170 patients (85 type 2 diabetics with nephropathy and 85 type 2 diabetics without nephropathy) and 91 healthy control subjects were enrolled in our study. I/D polymorphism of the ACE gene was detected by polymerase chain reaction (PCR) utilizing specific primers. Results: The frequency of DD genotype in the DN group was higher than that of the type 2 diabetic patients (30.6% vs. 20%, P =0.157) and the control group (30.6% vs. 14.3%, P=0.006). The frequency of D allele in nephropathic patients was 58.2% as compared to type 2 diabetic patients without nephropathy 50.5% (P=0.19) and control subjects 37.3% (P =0.001). Therefore, the frequency of DD genotype and D allele significantly increased in DN patients in comparison to healthy controls. Conclusion: It is concluded that the DD genotype and/or D allele of ACE gene may increase the risk for type 2 diabetes but not diabetic nephropathy.  相似文献   

4.
Summary The relationship between diabetic nephropathy and an insertion (I)/deletion (D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is still under debate. The association of ACE gene polymorphism with nephropathy and retinopathy was therefore examined in 362 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and 105 healthy control subjects. Distribution of the ACE genotype did not differ between healthy control subjects and diabetic patients without complications. However, the frequency of the D allele was significantly higher in the diabetic subjects with nephropathy than in those without (0.32 in normoalbuminuric patients vs 0.44 in albuminuria patients with albuminuria) (2=7.7; p=0.006). There was no significant association between ACE genotype and retinopathy. These observations thus demonstrate a significant association of the ACE gene polymorphism with nephropathy, but not with retinopathy, in Japanese patients with NIDDM.Abbreviations ACE Angiotensin-converting enzyme - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - UAI urinary albumin index - PCR polymerase chain reaction  相似文献   

5.
2型糖尿病肾病亚甲基四氢叶酸还原酶基因多态性研究   总被引:4,自引:1,他引:3  
目的探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate  相似文献   

6.
Summary Insulin-dependent diabetic (IDDM) patients with diabetic nephropathy have a highly increased morbidity and mortality from coronary heart disease. An insertion (I) /deletion (D) polymorphism in the angiotensin-I-converting enzyme (ACE) gene has been shown to be associated with coronary heart disease. Therefore, we have investigated the role of this ACE/ID polymorphism in 198 IDDM patients with diabetic nephropathy and 190 normoalbuminuric IDDM patients. The prevalence of myocardial infarction and other coronary heart disease was significantly elevated in patients with nephropathy, 19 % (38/198) vs 8 % (15/190), p < 0.001. In the nephropathic group 12 of 63 (19 %), 23 of 95 (24 %), and 3 of 40 (7.5 %) patients with the DD, ID and II genotypes, respectively had a history of coronary heart disease, II vs DD and ID, p < 0.05 when compared to nephropathic patients without coronary heart disease. Multiple logistic regression analysis of the risk factors associated with coronary heart disease in univariate analysis revealed that the II genotype acts as an independent protective factor against coronary heart disease, odds ratio II/DD + ID 0.27 (95 % confidence interval 0.07–0.97, p < 0.05). There was no difference in genotype or allele frequency (D/I) between patients with and without nephropathy, 0.56/0.44 in both groups, but plasma ACE concentration was elevated in patients with nephropathy 609 (151–1504) ng/ml as compared to patients with normoalbuminuria, 428 (55–1630) ng/ml, p < 0.001. We suggest that ACE/ID polymorphism may influence the frequency of life-threatening cardiac complications in IDDM patients suffering from diabetic nephropathy, a condition characterized by increased plasma ACE concentration. [Diabetologia (1995) 38: 798–803] Received: 10 October 1994 and in revised form: 20 December 1994  相似文献   

7.
血管紧张素Ⅰ转化酶(ACE)基因多态和2型糖尿病肾病(DN)的关系。方法用PCR技术检测102例中国汉族2型糖尿病患者ACE基因I/D多态基因型。结果DN组(n=36)和无DN组(n=49)相比,D型等位基因和DD基因型糖频率升高(分别为59.7%vs38.8%,X^2=7.30,33.3%vs12.2%,X^2=5.53),有显著性差异(P〈0.05),病程≤5年合并DN组(n=11)与病程〉5  相似文献   

8.
The aim of this study was to investigate whether an association exists between the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and microvascular complications of type 2 diabetes mellitus in Turkish patients. A total of 239 type 2 diabetic patients and 138 sex and age matched control subjects were included into the study. The I/D polymorphism was determined by polymerase chain reaction (PCR). Nephropathy status was determined according to urinary albumin/creatinine ratio (microg/mg) (<30 normoalbuminuria, 30-300 microalbuminuria, >300 macroalbuminuria) and retinopathy was evaluated by fundoscopic examination and by flourescein fundus angiography. The distribution of ACE I/D polymorphism and allele frequencies in diabetic patients were not significantly different from controls, DD genotype 32.2 versus 37.2%; ID genotype 50.6 versus 47.1%; and II 17.2 versus 15.2%; D allele 57.5 versus 61.2%; I allele 42.5 versus 38.8%. Genotype distribution between normo-, micro- and macroalbuminuric patients did not differ significantly (DD:ID:II (%), normoalbuminuria, 35:46:19; microalbuminuria, 28:55:17; macroalbuminuria, 31:55:14). There was also no difference in genotype distribution between patients with and without retinopathy (DD:ID:II (%), retinopathy positive, 32:51:17; retinopathy negative, 33:49:18). In conclusion, the ACE I/D polymorphism does not seem to be associated with diabetic nephropathy and retinopathy in Turkish type 2 diabetic patients.  相似文献   

9.
10.
2型糖尿病肾病与血管紧张素转换酶基因多态性的研究   总被引:11,自引:0,他引:11  
目的 探讨2型糖尿病肾病与ACE基因I/D多态性。方法 应用PCR方法检测了36例健康对照者、58例糖尿病肾病和50例有糖尿病肾病、病程大于5年的2型糖尿病病人的ACE基因I/D基因型。结果 三组间ACE基因II、ID、DD三种基因型和I、D两种等位基因的频率分布无显著性差异;在三种基因型之间,尿白蛋白排泄率和血肌酐水平也无显著性差异。结论 ACE基因I/D多态生与中国汉族2型糖尿病肾病无关联,A  相似文献   

11.
Twenty to forty percent of type-2 diabetic patients (DM2) present nephropathy. Genetic polymorphism of Apolipoprotein E (Apo E) has been proposed as a risk factor in the development and progression of diabetic nephropathy. The purpose of the study was to evaluate the relationship between Apo E polymorphism and presence of nephropathy in DM2 patients. We studied 85 DM2 patients with a similar nutritional state, environmental and socioeconomic condition and more than 10 years of evolution. They were grouped in DM2 patients with kidney complications (n=56) and without kidney complications (n=29; control group). Apo E genotype was determined by restriction fragment-length polymorphism analysis. A plasmatic biochemical characterization was performed on all the subjects studied. The 85 DM2 patients had arterial hypertension in treatment. The nephropathy diabetic group showed differences (p<0.001) in BMI, systolic blood pressure, glycemia, cholesterol (total, HDL and LDL), HbA1c and creatinine. The e4 allelic frequency was 8% in the nephropathy group versus 25.9% in the control group. Apo e3 allele and E3/3 genotype frequency were higher and E3/4 genotype was lower in the nephropathy group than in controls. These groups also showed differences in total, HDL and LDL cholesterol. DM2 patients without nephropathy presented a higher frequency of e4 allele. These results could suggest a protective role of e4 allele in the development and progression of diabetic nephropathy.  相似文献   

12.
Genetic factors are involved in the development of diabetic nephropathy in type-1 diabetes. We are examining the association of the angiotensin-converting enzyme (ACE), insertion/deletion (I/D) polymorphism with the presence of diabetic nephropathy in type-1 diabetic patients. 52 type-1 diabetic patients with diabetic nephropathy (30 with either microalbuminuria or macroalbuminuria and 22 with end stage renal disease on dialysis) were compared with 10 type-1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years and 27 non-diabetic healthy subjects. We found that the D-allele frequency was higher in patients with nephropathy than in the healthy and normoalbuminuric controls. There was an association in the DD polymorphism of the ACE gene with patients with diabetic nephropathy and not with the control subjects. We conclude that the DD genotype of ACE gene polymorphism is associated with diabetic nephropathy in patients with type-1 diabetes mellitus.  相似文献   

13.
OBJECTIVE: Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T(m)) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. RESULTS: The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively (P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively (P=.758). CONCLUSIONS: There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.  相似文献   

14.
OBJECTIVE: Genetic predisposition has been implicated in diabetic nephropathy (DN). The C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, may play a role in the development of not only vascular disease but also diabetic microangiopathies. In this study, we examined the distribution of the MTHFR genotypes in the Chinese population and the association between the C677T variant and diabetic nephropathy. METHODS: 220 unrelated patients with type 2 diabetes mellitus and 130 controls were recruited. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. RESULTS: In 130 healthy control subjects, the frequency of the mutant T allele was 30.0%, comparable to that of a Hong Kong (Chinese) population. The distribution of the three genotypes was as follows: TT genotype, 16.9%; CT genotype, 26.2%; and CC genotype, 56.9%. This genotype distribution did not differ between control subjects and type 2 diabetic patients in which 19.1% were TT, 34.5% were CT and 46.4% were CC (2=3.85, P>0.05). The frequency of the mutant T allele was 42.3% in diabetic patients with nephropathy (n=124) versus 28.6% in those without nephropathy (n=96). The genotype frequencies were TT, 21.0%; CT, 42.7%; CC, 36.3% in diabetic patients with nephropathy versus TT, 16.7%; CT, 23.9%; CC, 59.4% in those without nephropathy. The MTHFR genotype and allele frequencies were different between diabetic patients with and without nephropathy (chi2=12.27, P<0.005; chi2=8.77, P<0.005, respectively). Moreover, plasma homocysteine levels were markedly higher in individuals with TT genotype than those with CC or CT genotype. CONCLUSIONS: The C677T mutation of MTHFR gene is common in the Chinese population. MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels may represent a genetic risk factor for diabetic nephropathy in Chinese type 2 diabetic patients.  相似文献   

15.
The T/T genotype of the methylenetetrahydrofolate reductase C677 T gene polymorphism is associated with elevated homocysteine levels and presumably with increased atherosclerotic risk. We evaluated the interaction between this gene polymorphism and end-stage diabetic nephropathy on the observed prevalence of macroangiopathy in type 2 diabetes mellitus. The methylenetetrahydrofolate reductase 677 C/T genotypes were determined in 174 type 2 diabetic patients: 80 with and 94 without renal failure due to diabetic nephropathy. In the patients with renal failure, the T/T genotype and T allele were significantly associated with macroangiopathy (T/T; 31 % vs. 2 %, P = 0.0001 T allele; 59 % vs. 29 %, P = 0.00014), whereas the associations were not significant in the patients without renal failure. In the multiple logistic regression analysis, age (10 years OR 4.05 [1.79 - 9.31], P < 0.0005) and 677 T allele (6.84 [2.12 - 22.05], P = 0.0013) were significantly associated with macroangiopathy in the patients with renal failure. In conclusion, this study demonstrated that the 677 T/T genotype and T allele of MTHFR were significantly associated with macroangiopathy in type 2 diabetic patients with renal failure. The MTHFR 677 T allele, together with renal dysfunction due to diabetic nephropathy, could be a strong risk factor for atherosclerotic disease.  相似文献   

16.
OBJECTIVE: Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease, but the pathogenesis of this condition is not exactly understood. Several studies from different parts of the world have examined angiotensin-converting enzyme (ACE) gene polymorphism as a candidate for DN. Two studies yielding controversial results have been reported from India. To rule out this discrepancy, we carried out a hospital-based study on a cohort from our population to determine whether ACE gene polymorphism is associated with DN. RESEARCH DESIGN AND METHODS: ACE gene polymorphism was analyzed by polymerase chain reaction in 460 individuals consisting of 174 cases of DN, 175 cases of Type 2 diabetes mellitus (DM), and 111 controls. The DN cases included in the study were Type 2 DM cases with serum creatinine >1.5 mg/dl and serum albumin >30 mg/dl in a 24-h urine sample. RESULTS: ACE insertion/deletion genotyping analysis showed DD genotype in 22.75% of DN cases, 15.42% of Type 2 DM cases, and 21.62% of controls. Chi-square test between the DN group and the control group did not show a significant difference in D allele. However, the difference was significant at P<.05 between the DN group and the DM group. The odds ratio was 2.0953 (95% confidence interval=1.35-3.2522), indicating a significant association of DD genotype and D allele with DN. CONCLUSION: Our data enable us to conclude that Asian Indians with D allele and Type 2 DM are at greater risk for developing DN.  相似文献   

17.
In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.  相似文献   

18.
Diabetic nephropathy is the most frequent cause of end-stage renal failure. One of the crucial factors in a development of renal and cardiovascular complications of diabetes is genetic predisposition. The genes of the renin-angiotensin system are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was the evaluation of a possible role of genetic polymorphisms of some of the RAS system genes in the nephropathy in type 2 diabetes. The study was performed in 117 patients with diabetic nephropathy, compared with 200 healthy subjects as a control group. The following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme gene (ACE), M235T of the angiotensinogen gene (AGT) and A1166C of the angiotensin II type 1 receptor gene (AT1R) were evaluated by polymerase chain reaction (PCR). No statistically significant differences between groups were found in the allele frequency and genotype distribution for ACE and AGT polymorphisms. The results for the AT1R gene polymorphism revealed significant differences in allele and genotype frequencies. The homozygous CC genotype was more frequent in patients with diabetic nephropathy than in control group. Both genotypes with the C allele (AC + CC) were found in 56% of patients compared to 38% in control group. These results suggest increased susceptibility to diabetic nephropathy in individuals carrying the CC genotype. Therefore, the A1166C polymorphism of the AT1R gene could be a potential genetic marker for increased susceptibility to renal complications in type 2 diabetes.  相似文献   

19.
李长贵  杨乃龙 《山东医药》2002,42(17):16-18
为探讨 PAI- 1基因启动子区 4 G/ 5 G基因多态性、一氧化氮合酶 (e NOS)第 4内含子 2 7bp插入 /缺失 (a/b)多态性与糖尿病肾病 (DN)的相关性 ,采用发色底物法测定 PAI- 1活性 ;等位基因特异性引物 PCR扩增技术测定 PAI- 1基因 4 G/ 5 G多态性 ;聚合酶链反应测定 e NOS基因第 4内含子 2 7bp的 a/ b多态性。结果显示 ,Hb A1c、SBP、TC、e NOS基因第 4内含子 a/ b多态均属 DN的独立危险因素。早期糖尿病肾病组 (DN+组 ) a等位基因及 ab基因型频率显著高于糖尿病非肾病组 (DN-组 ) (P<0 .0 5 )。DN+组血浆 PAI- 1活性明显高于 DN-组 (P<0 .0 5 ) ;4 G纯合子组 PAI- 1活性明显高于 4 G/ 5 G杂合子及 5 G纯合子组 (P<0 .0 0 5 )。2型糖尿病患者中 ,4 G纯合子和a/ b杂合子携带者 DN的相对风险明显增加 (P<0 .0 5 ) ,4 G杂合子携带者 DN的相对风险增加不明显 (P>0 .0 5 )。当 a/ b杂合子和 4 G纯合子基因多态并存时 DN的发病风险明显增加。认为 PAI- 1基因启动子区 4 G/ 5 G基因多态、e NOS基因第 4内含子 a/ b多态与 DN的发生、发展有关。两种基因多态同时存在时 ,DN的发病风险明显增加  相似文献   

20.
目的研究白介素18(IL-18)基因型及血清水平与2型糖尿病肾病(DN)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360例2型糖尿病患者(160例伴DN)及180名正常对照组的IL-18的基因多态性,同时采用酶联免疫吸附试验(ELISA)检测血清IL-18水平。结果与对照组比较,糖尿病肾病组血清IL-18水平显著高于对照组(P〈0.01)。IL-18基因-137G/C多态性在两组人群中的分布差异有统计学意义(P〈0.05),携带-137C等位基因的糖尿病肾病患者血清IL-18水平显著高于不携带者(P〈0.05)。结论IL-18基因-137G/C多态性与DN的发病可能具有相关性,其中C等位基因可能是DN发病的遗传易感基因;携带C等位基因的个体可能通过促进IL-18的高度表达进而增加了DN的发病风险。  相似文献   

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