血管紧张素转换酶基因多态性与糖尿病及其肾脏合并症发病的关系

目的探讨血管紧张素转换酶（ＡＣＥ）基因插入／缺失（Ｉ／Ｄ）多态性与Ⅱ型糖尿病（ＮＩＤＤＭ）及其肾脏合并症发病的关系。方法应用聚合酶链反应（ＰＣＲ）扩增技术检测了１０９例ＮＩＤＤＭ患者及１５５例健康对照者的ＡＣＥ基因Ｉ／Ｄ多态性。结果位于ＡＣＥ基因第１６内含子的Ｉ／Ｄ多态性经ＰＣＲ技术扩增后分为三种基因型：纯合子缺失型（ＤＤ）,纯合子插入型（Ｉ）及杂合子插入／缺失型（ＩＤ）。１０９例ＮＩＤＤＭ患者与１５５例正常对照组之间基因型及等位基因频率差异均无显著意义;ＮＩＤＤＭ合并肾病者（ＤＮ）的基因型与未合并肾病者无显著性差异,但等位基因则有显著性差异（Ｄ、Ｉ等位基因为０４５和０５５对０３０和０７０）（Ｐ＜００２）;ＮＩＤＤＭ病程≤１年即伴有肾病者与病程≥５年仍无肾病者比较,ＤＤ型及Ｄ等位基因均显著高于无肾病组（Ｐ均＜００５）,后者以Ｉ型及Ｉ等位基因占绝对优势。结论ＡＣＥ基因多态性与ＮＩＤＤＭ发病无关,而与其肾脏合并症则明显相关,ＤＤ型是ＤＮ的易感基因,而Ｉ型则为其保护基因。     

河北地区汉族人血管紧张素转换酶基因与糖尿病肾病的相关性研究

目的探讨血管紧张素转换酶（ＡＣＥ）基因与糖尿病肾病（ＤＮ）发病的关系。方法用ＰＣＲ方法检测１４９例ＮＩＤＤＭ患者及１００例正常对照的ＡＣＥ基因型。结果（１）ＡＣＥ基因型及等位基因构成比在正常对照组和ＮＩＤＤＭ组间无统计学差异;（２）ＤＤ基因型及Ｄ等位基因频率在ＤＮ组（０２７）显著高于非ＤＮ组（００９）。结论ＡＣＥ基因多态性与ＤＮ发病有关。     

Excess of DD homozygotes in haemodialysed patients with type II diabetes. The Diabetic Nephropathy Study Group

The role of the insertion/deletion polymorphism of the angiotensin- converting enzyme (ACE) gene in the genesis of diabetic nephropathy has been controversial. It has recently been proposed that progression occurs more rapidly in individuals with diabetic and non-diabetic renal disease who are homozygous for the D allele. We studied 658 patients with type II diabetes, 347 without diabetic nephropathy and 311 with various stages of diabetic nephropathy, and determined the I/D polymorphism of the ACE gene. Patients at the extremes of renal risk, i.e. normotensive patients without antihypertensive treatment and without nephropathy (n = 144), vs patients on dialysis (n = 61), differed with respect to genotype (DD 36.8% vs 57.4%; P = 0.007) and allele frequencies (D 0.59 vs 0.76; P < 0.001). In contrast, patients with and without presumed nephropathy as assessed by albuminuria did not differ with respect to DD genotype. In conclusion, in this study, which was limited by sample size, patients with the highest renal risk more frequently had the DD genotype. This would be compatible with a greater risk of (or rate of) progression to end-stage renal failure.      

细胞间黏附分子1基因K469E多态性与2型糖尿病肾病的相关性研究

目的 探讨细胞间黏附分子1(ICAM-1) K469E基因多态性与2型糖尿病肾病(DN)的关系。方法 运用PCR-限制性多态性片断长度(RFLP)技术检测98名健康对照者和210例2型糖尿病患者(其中DN患者110例，DM患者100例)的基因型，比较各组的基因型和等位基因频率。结果 (1)DN组KK基因型和K等位基因频率显著高于DM组和正常对照组；(2)与EE型组相比，KK型组DN的发生率明显上升；(3)Logistic回归分析显示ICAM-1 K469E基因多态性是DN的危险因素。结论 ICAM-1 K469E多态性与2型糖尿病伴发肾病的发生有关，K等位基因可能是DN的易感基因。     

Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients.

BACKGROUND: Diabetic microvascular complications are the major causes of morbidity and early mortality in diabetes. Vascular endothelial growth factor (VEGF) is a potent multifunctional cytokine which plays a key role in the pathogenesis of diabetic microvascular complications. We examined the possible association of the VEGF gene polymorphisms with diabetic nephropathy and retinopathy in type 2 diabetes patients. METHODS: Genotyping of the VEGF gene insertion/deletion (I/D) and +405 polymorphisms was done by the polymerase chain reaction (PCR) and restriction fragment length polymorphism methods. A total of 426 patients with type 2 diabetes and 493 healthy subjects were genotyped. The frequency of VEGF alleles and genotype distribution were compared in diabetic and control groups. RESULTS: The distribution of the VEGF DD genotype was significantly different in patients with diabetic retinopathy compared with healthy controls, entire diabetic group and patients with no complications (44 vs. 23, 30 and 21%, respectively; P < 0.01). Such differences were not observed in the diabetic nephropathy group. The odds ratio for the D allele was 2.27 (95% CI 1.59-3.25). The multivariate logistic regression analysis revealed that the D allele of the VEGF gene I/D polymorphism was an independent risk factor of retinopathy (P < 0.001). The VEGF +405 genotype was not associated with diabetic complications in type 2 diabetes patients. CONCLUSION: Our study suggests that the I/D polymorphism in the promoter region of the VEGF gene is associated with retinopathy but not nephropathy in type 2 diabetes patients. The multivariate logistic regression analysis showed that the D allele of the VEGF polymorphism is an independent risk factor of diabetic retinopathy after controlling for other clinical variables.     

DD genotype of angiotensin-converting enzyme in type 2 diabetes mellitus with renal disease in Mexican Mestizos

Aim:   The DD genotype of angiotensin-converting enzyme (ACE) has been suggested as a major contributor of diabetic nephropathy in several populations. The purpose of the present study was to determine whether micro/macroalbuminuria is associated with ACE insertion/deletion (I/D) polymorphism in Mexican Mestizos with type 2 diabetes mellitus.
Methods:   A total of 435 patients with type 2 diabetes mellitus, of whom 233 had albuminuria, were characterized for the ACE I/D polymorphism by the polymerase chain reaction method.
Results:   Clinical and biochemical characteristics and frequencies according to DD, ID and II genotypes in patients with and without albuminuria showed no significant differences. However, only females with micro/macroalbuminuria showed higher frequency of a DD genotype than those without albuminuria (27.9%, 21.2% and 10.5%, respectively; P  ≤ 0.044). In addition, female patients with macroalbuminuria without dialysis showed no significant differences with patients undergoing dialysis.
Conclusion:   The ACE DD genotype is a risk factor for the development of renal disease in Mexican Mestizo females with type 2 diabetes, indicating a possible DD genotype-associated sex effect in renal disease.     

血管内皮生长因子基因多态性与糖尿病肾病的相关性研究

目的 探讨血管内皮生长因子(VEGF)-634G／C基因多态性与糖尿病肾病(DN)的关系。方法 运用PCR-限制性多态性片段长度(RFLP)技术检测98例健康对照者和216例2型糖尿病患者[其中DN患者104例，单纯2型糖尿病(DM)患者112例]的基因型，比较各组的基因型和等位基因频率。结果 (1)CC基因型者血清VEGFT水平高于CG及GG型者；(2)DN组CC基因型和C等位基因频率显著高于DM组和正常对照组；(3)与GG型和CG型组相比，CC型组DN的发生率明显上升；(4)Logistic回归分析显示VEGF、VEGF基因多态性、收缩压(SBP)、HbA1c、LDL-C、体重指数(BMI)是DN的危险因素。结论 VEGF-63gG／C多态性与2型DM伴发肾病的发生有关，C等位基因可能是DN的易感基因。     

血管紧张素-Ⅰ转换酶基因多态性与糖尿病及糖尿病肾病的关系

目的　探讨血管紧张素Ⅰ转换酶基因（ＡＣＥ基因） 多态性与糖尿病及糖尿病肾病（ＤＮ） 的易感性之间的关系。方法　应用聚合酶链式反应（ＰＣＲ）方法扩增４８ 例正常人、７４ 例胰岛素依赖型糖尿病（ＩＤＤＭ） 患者（ 其中４０ 例不伴ＤＮ,３４ 例合并ＤＮ） 、１０２ 例非胰岛素依赖型糖尿病（ＮＩＤＤＭ） 患者（５７ 例不伴ＤＮ,４５ 例伴ＤＮ） 的ＡＣＥ基因上２８７ｂｐ 片断,根据插入（Ｉ） 或缺失（Ｄ） 来判断其多态性。结果　健康对照组与ＩＤＤＭ 及ＮＩＤＤＭ 组ＡＣＥ 等位基因、基因型均无显著性差异（ Ｐ＞０－０５）;在ＩＤＤＭ 组中,Ｄ等位基因及ＤＤ基因型在伴ＤＮ亚组中显著升高;在ＮＩＤＤＭ 组中,与不伴ＤＮ者比较,伴ＤＮ者其Ｉ等位基因、ＩＩ基因型频率明显为低。结论ＡＣＥ 基因多态性与糖尿病易感性无关,与ＤＮ密切相关。     

Higher frequency of apolipoprotein E2 allele in type 2 diabetic patients with nephropathy in Taiwan

BACKGROUND: Diabetes is one of the major causes of end stage renal failure in Taiwan. Previous studies have indicated that lipid abnormalities might contribute to the development and progression of diabetic nephropathy (DN). Apolipoprotein E (apo E) regulates the metabolism of lipoproteins. Three different apo E alleles (epsilon2, epsilon3 and epsilon4) produce apo E isoproteins, apo E2, apo E3 and apo E4. Thus, the apo E gene polymorphism may be associated with DN. METHODS: To investigate the distribution of apo E genotype in type 2 diabetic Taiwanese, we examined 314 patients with type 2 diabetes (100 without nephropathy and 214 with nephropathy) and 150 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. The apo E gene polymorphism was analyzed by polymerase chain reaction. RESULTS: Our study found that the frequency of apo E2 allele was significantly higher in the diabetics with nephropathy- non-dialysis group (7.7%) and diabetics with nephropathy- dialysis group (7.7%) than in normal controls (1.7%) (p < 0.001) and diabetics without nephropathy (2.0%) (p < 0.01). The E3 and E4 allele frequencies were not significantly different among groups. CONCLUSION: These findings imply that apo E polymorphism is apparently related to the development of DN in type 2 diabetes in Taiwan.     

ACE gene polymorphism and the prognosis and treatment of overt diabetic nephropathy

An insertion (I)/deletion (D) polymorphism of the angiotensin-converting-enzyme (ACE) gene influences the circulating and renal activity of the renin-angiotensin-aldosterone system. This Practice Point commentary discusses a 2008 paper by Parving et al. that analyzed the interaction between losartan and the I/D polymorphism in patients in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. The investigators found that patients with type 2 diabetes and proteinuria who have the D allele have an unfavorable renal prognosis, which is improved by losartan treatment (vs placebo) when given together with conventional antihypertensive treatment. No significant improvement in outcomes was observed in losartan-treated patients with the II genotype. Previous observational studies had suggested a decreased beneficial effect of ACE inhibitors in patients with type 1 diabetic nephropathy who have the DD genotype. Prospective studies in this area are needed before I/D genotype characterization can be used to guide the choice of therapy in patients with diabetes and proteinuria.     

Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy

We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32± 1.42 versus 0.75±0.78 g/day; P=0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45±1.50 versus 0.63±0.56 g/day; P=0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children. Received: 21 July 2000 / Revised: 8 December 2000 / Accepted: 11 December 2000     

The angiotensin-converting enzyme DD genotype is associated with glomerulopathy lesions in type 2 diabetes.

Genetic factors are important in conferring diabetic nephropathy (DN) risk. The insertion/deletion (I/D) polymorphism of the ACE gene has been described to be associated with DN risk and progression. The renal lesions underlying DN in type 2 diabetes are heterogeneous; only a subset of patients, characterized by a faster decline of renal function, have diabetic glomerulopathy. This study explored the relations between diabetic glomerulopathy and the ACE genotype distribution in 77 type 2 diabetic patients with an albumin excretion rate > or = 20 microg/min. Using morphometric analysis of kidney biopsies, mesangial and mesangial matrix fractional volumes [Vv(mes/glom) and Vv(MM/glom)] and glomerular basement membrane (GBM) width were estimated. We found that 13 patients were II, 30 were ID, and 34 were DD. Clinical features and renal function were similar in the three groups; in contrast, the DD patients had the highest Vv(MM/glom) and GBM width. Subdividing patients in tertiles of GBM width and Vv(MM/glom), from the lowest (I) to the highest (III) values, the DD carriers had an odds ratio of 6.11 (95% CI 1.84-20.3) and 10.67 (2.51-45.36), respectively, for the likelihood of being in tertile III than I for GBM width and Vv(MM/glom). Multiple regression analysis revealed the I/D polymorphism as an independent determinant of GBM thickening in addition to diabetes duration and HbA(1c). In conclusion, the ACE DD genotype is associated with diabetic glomerulopathy lesions, making the study of this polymorphism helpful in identifying those type 2 diabetic patients at higher risk of fast DN progression.     

Angiotensin-converting enzyme polymorphism gene and evolution of nephropathy to end-stage renal disease

Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of nephropathy and end-stage renal disease (ESRD). The association between angiotensin-converting enzyme (ACE) gene polymorphism and nephropathy evolution was studied. A random sample of 161 subjects from the Nephrology Department (of Hospital de Sant Pau) were divided into two groups: (i) 117 with end-stage renal disease; (ii) 44 with established nephropathy; and (iii) control groups of 129 subjects. The ACE gene polymorphism was performed by using polymerase chain reaction. High DD genotype presentation was observed in the two groups of subjects with nephropathy (46.12 and 61.37%, respectively vs 35.66% in controls; P < 0.0482), and also, a decrease was observed in the II genotype (6.4 and 4.54%, respectively vs 13.17% in controls, P < 0.0404). Glomerular filtration rate (GFR) was evaluated after 44 months of follow up. An important decrease of GFR was observed in patients with DD polymorphism versus other genotypes (initial, 32.3 +/- 7.9 and at 44 months, 18.35 +/- 3.3 mL/min vs 31.4 +/- 11.9 and 11.7 +/- 3.2 mL/min; P < 0.039). In a non-longitudinal study of patients in ESRD, patients with an ACE-DD genotype had a lower period of time between diagnosis of nephropathy and ESRD than patients with other genotypes (10.45 +/- 9.32 vs 19.5 +/- 8.4 years; P < 0.034). In conclusion, the ACE gene that controls RAS response may influence the development and progression of nephropathy to ESRD. Patients who develop several types of nephropathy have a higher risk of severe evolution if they have a profile of ACE-DD genotype.     

Prognostic value of angiotensin-I converting enzyme I/D polymorphism for nephropathy in type 1 diabetes mellitus: a prospective study

Angiotensin-I converting enzyme (ACE) regulates renal hemodynamics. Its insertion/deletion (I/D) polymorphism, which determines most of ACE interindividual variance, was proposed as a genetic marker for diabetic nephropathy. A substitution (M235T) polymorphism in angiotensinogen (AGT) may interact with ACE I/D polymorphism for the risk of diabetic nephropathy, but their prognostic values have to be established by follow-up studies. A total of 310 type 1 diabetes mellitus patients who attended the diabetic clinic in Angers (France) took part in a prospective, observational, follow-up study. Glycohemoglobin, BP, plasma creatinine, and urinary albumin excretion were determined periodically. Nephropathy was classified as absent, incipient (microalbuminuria), established (proteinuria), advanced (plasma creatinine > or = 150 micromol/L), and terminal (renal replacement therapy). The main end point was the occurrence of a renal event defined as the progression to a higher stage of diabetic nephropathy. At baseline, 251 (81%) patients had no nephropathy, 35 (11%) had incipient nephropathy, 18 (6%) had established nephropathy, and 6 (2%) had advanced nephropathy. The ACE I/D and M235T AGT polymorphisms were in Hardy-Weinberg equilibrium in the patients. The median duration of follow-up was 6 yr (range, 2 to 9 yr). The occurrence of renal events was significantly influenced by ACE genotype (log-rank II versus ID versus DD, P < 0.03) with a dominant deleterious effect of the D allele: ID or DD versus II (adjusted hazard ratio, 5.0; 95% confidence interval, 1.5 to 16.6). Other contributors were high glycohemoglobin and systolic BP. In the patients who initially were free of nephropathy, baseline plasma ACE concentration was higher in patients who progressed to microalbuminuria (571 +/- 231 versus 466 +/- 181 microg/L; P = 0.0032); the D allele independently favored the occurrence of incipient nephropathy (adjusted hazard ratio, 4.5; 95% confidence interval, 1.1 to 19.4); other contributors were male gender, baseline systolic BP, and urinary albumin excretion. The AGT M235T polymorphism was not associated with renal events. The D allele of the ACE I/D polymorphism is an independent risk factor for both the onset and the progression of diabetic nephropathy in type 1 diabetes mellitus patients.     

Association of the DD genotype and development of Japanese type 2 diabetic nephropathy.

We determined the insertion/deletion (I/D) polymorphism of the angiotensin-coverting enzyme (ACE) gene in a multicenter trial of ethnically homogeneous Japanese type 2 diabetes mellitus (DM) patients. All patients (n = 748) were divided into 5 groups as follows: group I (normoalbuminuric patients), group II (microalbuminuric patients), group III (overt albuminuric patients with serum creatinine (s-Cr) levels of less than 1.2 mg/dl), group IV (overt albuminuric patients with s-Cr levels of more than 1.3 mg/dl but excluding hemodialysis patients), and group V (hemodialysis patients). We selected patients with a diabetic duration of more than 15 years in the mild stage (groups I and II), but placed no limits on those in the advanced and end-stages (groups III, IV and V). The frequency of the DD genotype was slightly higher in the advanced and end stages. The frequency of the DD genotype in the mild stage differed from that in the end stage (II/ID/DD 47.8%/41.0%/11.2% vs. 37.0 %/43.3%/19.7% p = 0.07, II + ID/DD 88.8%/11.2% vs. 80.3%/19.7%, p < 0.05). D allele frequency in the mild stage also differed from that in the end stage (I/D 68.3%/31.7% vs. 58.7%/41.3%, p < 0.02). The presence of the DD genotype increased the risk of end-stage renal disease (ESRD) more than that of the other genotypes (odds ratio ID/II = 1.37, 95% CI 0.82-2.27; DD/II = 2.27, 95% CI 1.12-4.61). It appears that the DD genotype is associated with progression of Japanese type 2 diabetic nephropathy.     

血管紧张素转化酶基因多态性在终末期肾功能衰竭患者中的分布及其意义

目的 为了进一步阐明由于血管紧张素(ACE)基因多态性而导致的循环中ACE水平不同在肾脏疾病进展中的意义。方法 对77例终末期肾功能衰竭(ESRF)患者和150名正常人ACE基因多态性进行了分析。结果 ACE基因缺失型(DD)(15.6％VS.6.0％,P<0.01)和插入型(DI)(53.2％VS39.3％,P<0.05)在ESRF患者中的发生频率明显高于正常人,而Ⅱ型的发生频率则明显低于正常人(31.2％VS54.7％,P<0.01)。结论 ACE基因多态性与肾脏疾病病情进展及肾小球硬化的发生有一定联系。ACE基因多态性的分析,有可能成为判断肾脏疾病患者预后的一个标记物。     

Polymorphism of the aldosterone synthase gene is not associated with progression of diabetic nephropathy, but associated with hypertension in type 2 diabetic patients

Aim: Inhibition of aldosterone system is beneficial in diabetic nephropathy, and aldosterone synthesis is regulated at the gene-encoding aldosterone synthase (CYP11B2). Considering the role of aldosterone in diabetic nephropathy, genetic polymorphism of this gene may contribute to the development and progression of diabetic nephropathy. In this study, we investigated whether it is associated with diabetic nephropathy in type 2 diabetic patients. Methods: 197 type 2 diabetic patients and 71 healthy controls were enrolled. The study subjects were divided into four groups: healthy controls with normoalbuminuria (n = 71), normoalbuminuric diabetic group (n = 71), microalbuminuric diabetic group (n = 51) and overt proteinuria group (n = 51). Polymorphism of aldosterone synthase gene was determined using standard PCR technique. Results: Higher frequency of TT genotype and T allele in steroidogenic factor-1 (SF-1) binding site and wild type (WT) in intronic conversion (IC) in CYP11B2 was observed in diabetic patients than controls. However, there was no significant difference in SF-1 and IC genotype among diabetic patients according to the state of diabetic nephropathy. Subgroup analysis based on SF-1 polymorphism demonstrated that TT genotype is associated with higher systolic and diastolic blood pressure and higher plasma aldosterone level. In addition, WT in IC genotype showed a significantly higher urinary albumin excretion rate. Plasma aldosterone level was significantly related with systolic blood pressure. Conclusion: Our study suggests that aldosterone synthase gene polymorphism is not associated with progression of diabetic nephropathy, but it may contribute to the development of hypertension associated with increased aldosterone secretion in type 2 diabetic patients.     

2型糖尿病肾病患者p22phox基因多态性的研究

目的研究NADPH氧化酶p22phox亚基基因多态性与中国上海汉族人群2型糖尿病肾病（DN）相关性。方法应用限制性片断长度多态性（RFLP）-PCR方法对105例健康对照组和194例2型糖尿病（DM）患者（其中71例DN）进行p22phox亚基C242T、A640G基因型检测。同时检测其身高、体重、血压、血脂、空腹血糖及胰岛素、HbAlc的水平。结果DN组CT＋TT基因型频率明显高于2型DM和对照组（26．76％比17．07％、3．81％，P=0．0002）；DN组T等位基因频率明显高于2型DM和对照组（22．54％比13．42％、2．86％，P=0．0001）；3组间AA基因型频率与A等位基因频率差异无统计学意义。多元回归分析显示，T242等位基因、收缩压、空腹血糖、HbAlc、β细胞功能指数（Homa-IS）是DN的危险因素。结论p22phox亚基T242等位基因变异可能是中国上海地区汉族人群DN的易感基因：而p22phox亚基A640G基因多态性与上述人群DN无相关性。T242等位基因、收缩压、空腹血糖、HbAlc、Homa-IS是DN的危险因素。     

Role of GLUT1 gene in susceptibility to diabetic nephropathy in type 2 diabetes

BACKGROUND: The XbaI polymorphism in the glucose transporter GLUT1 gene has been implicated in the development of diabetic nephropathy in Chinese type 2 diabetes patients. METHODS: To examine whether the XbaI polymorphism is involved in the development of diabetic nephropathy in Caucasian type 2 diabetes patients, a large case control study was performed. The study group of 444 patients with type 2 diabetes consisted of three subgroups: 162 patients with normoalbuminuria (only patients with duration of type 2 diabetes of at least 10 years after diagnosis); 150 with microalbuminuria; and 132 subjects with persistent proteinuria or chronic renal failure (CRF). The polymerase chain reaction (PCR)-based genotyping of the XbaI polymorphism was performed in each subject. RESULTS: The genotype distribution in the subgroups showed an increased frequency of the (+/+) genotype in patients with microalbuminuria (41%; OR 1.40, 95% CI, 0.89 to 2.24) and proteinuria/CRF (47%; OR 1.82, 95% CI, 1.13 to 2.93, P = 0.013) when compared with normoalbuminuria (33%). No difference in the genotype distribution was observed between type 2 diabetes patients and healthy controls. CONCLUSIONS: The results of this study in Caucasian patients with type 2 diabetes indicate that the XbaI(-) allele in the GLUT1 gene protects against the development of diabetic nephropathy. Our results are in contrast to the case control study in Chinese patients with type 2 diabetes in which the presence of the XbaI(-) allele appeared to have a strong association with the development of diabetic nephropathy.     

Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients-- interaction with ACE insertion/deletion polymorphism

Angiotensin-converting enzyme (ACE) insertion(I)/deletion (D) polymorphism may modify the effect of inhibition of the renin-angiotensin-aldosterone system (RAAS) on survival and cardiorenal outcomes in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (+/- standard deviation) age of 59.7 +/- 13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 (interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality (HR 0.34 (0.23, 0.50)) and renal end point (HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection (II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 (0.25, 0.72) vs 0.95 (0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers.