Angiotensin-converting enzyme gene polymorphism and the progression rate of focal segmental glomerulosclerosis in Iranian children

Aim: Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of glomerulonephritis leading to end-stage renal disease (ESRD). A few clinical and paraclinical factors are considered as contributing factors in progression rate. However, there are controversial reports on the relationship between ACE gene polymorphism and rapidity of progression of FSGS to ESRD in different populations. To elucidate this issue, we investigated the relationship between the insertion (I) and deletion (D) ACE gene polymorphism and rapidity of progression of FSGS to ESRD in Iranian children. Methods: Forty-one children aged 1–18 years admitted to St AlZahra Hospital, Isfahan, and St Ali Asghar Hospital, Tehran, Iran, with idiopathic FSGS were enrolled. Renal death was defined as a glomerular filtration rate (GFR) of less than 50 mL/min per 1.73 m² or a decreased GFR to less than 50% compare to baseline. Reaching renal death in less or more than 2 years were labelled as rapid progressors (RP) or slow progressors (SP), respectively. Intron 16 of the ACE gene was amplified by the polymerase chain reaction technique. Results: Twenty-eight patients were male and 13 were female. In 15 RP patients, the genotype distribution was 26.6% DD, 6.7% II and 66.7% ID. In 26 SP patients, the genotype was similar (38.6% DD, 7.6% II and 53.8% ID, P > 0.05). There were no statistically significant differences for ACE I/D gene polymorphism between the two groups of patients (P > 0.05). Conclusion: Our study revealed no correlation between ACE I/D gene polymorphism and rapidity of progression of FSGS to ESRD in Iranian children.     

Insertion/Deletion (I/D) Polymorphism of Angiotensin-Converting Enzyme Gene in Steroid-Resistant Nephrotic Syndrome for Children: A Genetic Association Study and Meta-analysis

Abstract

An assessment of the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with steroid-resistant nephrotic syndrome (SRNS) risk in children is still controversial. A meta-analysis was performed to evaluate the relation between ACE gene polymorphisms and SRNS susceptibility. The relevant studies were screened from electronic database and eligible investigations were synthesized using meta-analysis methods. Seven investigations were identified for the analysis of association between ACE I/D gene polymorphism and SRNS risk in children, including five in Asians, one in Caucasians, and one in Africans. There was not a markedly positive association between D allele or DD genotype and SRNS susceptibility in Asians (OR = 1.60, p = 0.26; OR = 1.90, p = 0.38) and for Caucasian population (OR = 0.92, p = 0.86; OR = 0.27, p = 0.22). However, an association of D allele with SRNS susceptibility was observed (OR = 4.67, p = 0.003) in Africans, but not for DD genotype (OR = 6.00, p = 0.05). Interestingly, II genotype seemed to play a positive role against SRNS onset for Asians and African children (OR = 0.51, p = 0.02; OR = 0.07, p = 0.02), but not for Caucasians (OR = 0.33, p = 0.30). In conclusion, our results indicate that D allele or DD homozygous might not be a significant genetic molecular marker for the development of SRNS in Asians and Caucasian children. However, D allele seemed be associated with SRNS risk for Africans but DD genotype did not.     

A meta-analysis of the association of G915C,G800A,C509T gene polymorphism of transforming growth factor-β1 with diabetic nephropathy risk

This meta-analysis was conducted to evaluate the association of transforming growth factor-β1 (TGF-β1) G915C, G800A, C509T gene polymorphism with the risk of diabetic nephropathy (DN). The association literatures were identified from PubMed, Cochrane Library, and CBM-disc (China Biological Medicine Database) on March 1, 2013, and eligible reports were recruited and synthesized. Seven reports were recruited into this meta-analysis for the association of TGF-β1 G800A, C509T, G915C gene polymorphism with DN risk. GG genotype, CC genotype, and C allele of TGF-β1 G915C were not associated with the DN risk (GG: OR?=?0.84, 95% CI: 0.62–1.14, p?=?0.27; CC: OR?=?1.05, 95% CI: 0.50–2.22, p?=?0.90; C allele: OR?=?1.16, 95% CI: 0.88–1.51, p?=?0.29). Furthermore, TGF-β1 G800A, C509T gene polymorphism was not associated with the DN risk. In conclusion, TGF-β1 G915C, G800A, and C509T gene polymorphism are not associated with the DN risk. However, more studies should be performed to confirm this relationship in the future.     

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy (T2DN) risk is still unclear. This study was performed to evaluate if there is an association between the MTHFR A1298C gene polymorphism and T2DN risk using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library on 1 October 2013, and eligible studies were included and synthesized. Eight reports were recruited into this meta-analysis for the association of the MTHFR A1298C gene polymorphism with T2DN risk. The MTHFR A1298C C allele or CC genotype was shown to be not associated with T2DN risk (C allele: OR?=?0.76, 95% CI: 0.43–1.34, p?=?0.34; CC genotype: OR?=?1.18, 95% CI: 0.63–2.22, p?=?0.60). Interestingly, AA genotype was associated with the T2DN risk (OR?=?0.68, 95% CI: 0.49–0.96, p?=?0.03). In the sensitivity analysis according to the Hardy–Weinberg equilibrium (HWE), the results were consistent with those in non-sensitivity analysis. However, in the sensitivity analysis according to the control source from hospital, sample size of case (≥100), sample size of case (<100), the MTHFR A1298C gene polymorphism was not associated with T2DN risk. In conclusion, the MTHFR A1298C gene polymorphism was not associated with T2DN risk. However, additional studies are required to firmly establish a correlation between the MTHFR A1298C gene polymorphism and T2DN risk.     

DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population

Abstract

DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to end-stage renal disease (ESRD). We aimed to determine the association of polymorphisms in xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1) with ESRD development. Polymorphisms in XPD codons 312 and 751 and XRCC1 codon 399 were genotyped in 98 patients undergoing hemodialysis and 102 healthy controls using polymerase chain reaction and restriction fragment length polymorphism. Patients having XRCC1-399 Arg/Gln genotype or XRCC1-399 Gln/Gln genotype had a significantly higher risk of ESRD than those with XRCC1-399 Arg/Arg [odds ratio (OR): 2.48; 95% confidence intervals (CI): 1.36–4.52; p?=?0.004 and OR: 4.05; 95% CI: 1.19–13.73; p?=?0.03, respectively]. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls (OR: 2.22; 95% CI: 1.16–4.25; p?=?0.02). Combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with Asp/Asn or Asn/Asn genotypes of XPDAsp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. Haplotypes association showed that association of Gln allele of XRCC1 Arg399Gln polymorphism with the Asn allele of XPDAsp312Asn polymorphism (p?=?0.004) or Gln allele of XRCC1 Arg399Gln polymorphism with the Gln allele of XPD Lys751Gln polymorphism (p?=?0.003) was highly significantly associated with the development of ESRD. This study revealed that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of ESRD. Furthermore, larger studies should be conducted to confirm these results.     

Association of angiotensin-converting enzyme insertion/deletion polymorphism with type 1 diabetic nephropathy: a meta-analysis

Objective: This study aimed to systematically evaluate the effect of an angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism on type 1 diabetic nephropathy (DN).

Methods: Cochrane Library, Embase, PubMed, Science Direct, Web of science, Wanfang data, VIP database, China Knowledge Resource Integrated Database, and SinoMed were searched. A total of 17 case–control studies analyzing ACE I/D polymorphism and type 1 DN risk were included in the present meta-analysis.

Results: Overall, a significant increased risk was found in allele comparison (OR?=?1.16, 95% CI?=?1.05–1.28, p?=?0.04), dominant comparison (OR?=?1.56, 95% CI?=?1.14–2.15, p?=?0.006) and homozygote comparison (OR?=?1.52, 95% CI?=?1.06–2.19, p?=?0.02). In subgroup analyses according to ethnicity, the risk of type 1 DN in Asian population was increased in allele comparison (OR?=?1.98, 95% CI?=?1.15–3.42, p?=?0.01), recessive comparison (OR?=?2.48, 95% CI?=?1.51–4.10, p?=?0.0004), dominant comparison (OR?=?3.15, 95% CI?=?1.90–5.23, p?p?=?0.05). However, there was no association between the ACE I/D genetic variants and type 1 DN in Caucasian populations.

Conclusions: Our meta-analysis results indicate that the ACE I/D polymorphism may contribute to type 1 DN development, especially in the Asian groups with type 1 diabetes. The current findings need to be confirmed by future well-designed and larger sample size primary studies in populations with different ethnicities.     

Influence of angiotensin I-converting enzyme polymorphism on development of post-transplant erythrocytosis in renal graft recipients

Abstract: Background: Post‐transplant erythrocytosis (PTE) is estimated at 5–20%. Angiotensin II generated by angiotensin I‐converting enzyme (ACE) stimulates erythropoiesis. The highest activity of ACE is observed in DD genotype. The question arises if ACE gene polymorphism influences PTE. Methods: One‐year prospective study included 89 kidney recipients (28 women and 61 men). Results: Thirty‐four (38%) recipients proved to be DD genotype, 36 (40%) ID, and 19 (22%) II genotype. Absolute PTE [hematocrit level (HCT) >50% and RBC > 5.5 mln/mm³] was found in 14 (19%) patients. PTE developed 6–12 months after kidney Tx. There were no significant differences in genotype distribution between patients with and without PTE. ANOVA showed that the most significant predictor of PTE development was the time since kidney Tx (p < 0.0001). Analysis of logistic regression showed that male sex was the most important factor in PTE development 12 months after kidney Tx (OR = 13.6: 95% CI 1.2–150.9, p < 0.05). D allele increased the PTE risk (OR = 3.3 for each allele: 95% CI 1.1–10.4, p < 0.05), the use of angiotensin‐converting enzyme inhibitors (ACEI) decreased the PTE risk (OR = 0.15: 95% CI 0.03–0.85, p < 0.05). In patients with DD genotype, there was a correlation between hemoglobin, RBC and HCT concentration, 12 months after Tx and panel of reactive antibody value before Tx (Rs = +0.43, p < 0.05). Conclusions: Male sex and D allele presence increase the risk of PTE development, especially in highly immunized patients. The use of ACEI decreases the risk of PTE development.     

Renin-angiotensin system polymorphisms in Taiwanese primary vesicoureteral reflux

We studied the angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1R) gene polymorphisms for association with susceptibility to primary vesicoureteral reflux (VUR) and disease progression in 74 Taiwanese children, including 16 with end-stage renal disease (ESRD), and 117 normal controls. Polymerase chain reaction-amplified products containing the ACE gene T-5491C, A-5466C, T-3892C, A-3692C, A-240T, Alu I/D, the AGT gene C-532T, G-217A, G-152A, A-20C, A-6G, T174M, T235M, and the AT1R gene A-1138T, T-810A, T-713G, C-521T, AG-214CC, A-153G, A1166C polymorphisms were analyzed by restriction enzyme digestion, gel electrophoresis, or single-strand conformation polymorphism analysis. All the polymorphisms examined were in Hardy-Weinberg equilibrium. The strong non-random association within the ACE, AGT, and AT1R genes suggests low levels of intragenic recombination. None of these polymorphisms showed association with VUR susceptibility. However, the allele frequency distribution of the six ACE polymorphisms among primary VUR patients with or without ESRD was statistically different. The linked ACE T-A-T-A-A-I allele was observed significantly more frequently in VUR children with ESRD (P<0.001). A significant increase of left ventricular mass index was also found in the linked ACE T-A-T-A-A-I allele group compared with the non-ACE T-A-T-A-A-I allele group of patients aged 18 years with renal progression. The AGT A-6G genotype frequencies were significantly different when the analysis was stratified by genotype of the ACE polymorphisms. The data showed that ACE gene polymorphisms were associated with progressive renal deterioration in Taiwanese children with VUR and might act synergistically with the –6 G allele of the AGT gene.Kuo-Pao Liu and Ching-Yuang Lin contributed equally to this work     

Association of angiotensin I-converting enzyme gene insertion/deletion polymorphism and IgA nephropathy: a meta-analysis

BACKGROUND/AIMS: The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been extensively examined for the association with immunoglobulin A (IgA) nephropathy (IgAN), however, conflicting results have occurred. We performed a meta-analysis to evaluate the association of ACE I/D polymorphism with IgAN in different ethnic groups. METHODS: 11 studies testing the association between ACE I/D polymorphism and IgAN susceptibility, and 9 studies testing the association of ACE I/D with IgAN progression were used in this analysis. The overall odds ratio (OR) was estimated by a fixed or random effect model. RESULTS: The overall OR for the risk of susceptibility and progression of IgAN in Asians for the DD genotype is 2.37 (95% CI 1.04-5.41) and 1.75 (95% CI 1.24-2.56). The overall OR for the D allele in Asians also showed a similar magnitude, though without statistical significance (p = 0.09, p = 0.13, respectively). In Caucasians, both the DD genotype and D allele were associated with IgAN progression (OR 1.90, 1.61, respectively), but not IgAN susceptibility (p = 0.30, p = 0.41, respectively). CONCLUSION: Our findings support the notion that ACE I/D polymorphism is associated with IgAN. Meanwhile, the role of ACE I/D polymorphism in Asians is different from that of Caucasians.     

Insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme gene in steroid-resistant nephrotic syndrome for children: a genetic association study and meta-analysis

An assessment of the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with steroid-resistant nephrotic syndrome (SRNS) risk in children is still controversial. A meta-analysis was performed to evaluate the relation between ACE gene polymorphisms and SRNS susceptibility. The relevant studies were screened from electronic database and eligible investigations were synthesized using meta-analysis methods. Seven investigations were identified for the analysis of association between ACE I/D gene polymorphism and SRNS risk in children, including five in Asians, one in Caucasians, and one in Africans. There was not a markedly positive association between D allele or DD genotype and SRNS susceptibility in Asians (OR = 1.60, p = 0.26; OR = 1.90, p = 0.38) and for Caucasian population (OR = 0.92, p = 0.86; OR = 0.27, p = 0.22). However, an association of D allele with SRNS susceptibility was observed (OR = 4.67, p = 0.003) in Africans, but not for DD genotype (OR = 6.00, p = 0.05). Interestingly, II genotype seemed to play a positive role against SRNS onset for Asians and African children (OR = 0.51, p = 0.02; OR = 0.07, p = 0.02), but not for Caucasians (OR = 0.33, p = 0.30). In conclusion, our results indicate that D allele or DD homozygous might not be a significant genetic molecular marker for the development of SRNS in Asians and Caucasian children. However, D allele seemed be associated with SRNS risk for Africans but DD genotype did not.     

Vitamin D receptor genetic variants among patients with end-stage renal disease

Back ground and objectives: Vitamin D receptor (VDR) gene polymorphism is reported to be associated with end-stage renal disease (ESRD). We have investigated the potential role of VDR gene polymorphisms among ESRD. Design and methods: The influence of VDR gene polymorphism in 258 ESRD patients comprising of 226 (87.5%) male and 32 (12.5%) females was investigated in this study. We compared ESRD patients with 569 healthy controls. The distribution of male and female among controls was 485 (85.3%) males and 84 (14.7%) females. This polymorphism was studied by using polymerase chain reaction (PCR). The product was digested by using restriction enzymes Apa1, Taq1, Fok1, and Bsm1. Results: We observed a significant difference in the genotype frequencies of the Apa1-aa (p = 0.0001, OR = 2.1, 95% CI = 1.45–3.08), Fok1-ff (p = 0.001, OR = 3.44, 95% CI = 1.76–6.76), and Bsm1-BB (p = 0.0004, OR = 6.8, 95% CI = 2.2–21.58). At allelic level B allele of Bsm1 was significantly different among ESRD patients as compared to controls (p = 0.0001). The combined analysis revealed that ESRD patients with Fok1 and Bsm1 polymorphism were at increased risk of 4.33-fold. The haplotype analysis revealed individuals with a/t/F/b haplotype were at greater risk of 11.0-fold (95% CI = 1.38–87.69). The serum calcium levels were significantly higher (p = 0.001) in Bsm1 “BB” genotype. Interpretations and conclusions: Bsm1 and Fok1 gene polymorphism of VDR gene were associated with ESRD among north Indians.     

Association of endothelial nitric oxide synthase gene polymorphisms with end-stage renal disease: a systematic review and meta-analysis

Background and objective: Endothelial nitric oxide synthase (eNOS) is one of the potent regulators of intra renal hemodynamics. Polymorphisms of eNOS gene may be involved in the progression of renal disease, and may be the causative factors that contribute to the deterioration of renal functions. During the past decades, several studies investigated the association of eNOS polymorphisms with the risk of end-stage renal disease (ESRD), but the results remain unclear and the mechanisms are not defined. Our study was designed to examine the role of different eNOS genetic polymorphisms in the progression of ESRD. Materials and methods: Relevant studies were identified through PubMed, Embase, Medline and CNKI (China National Knowledge Infrastructure) database published between January 2000 and November 2013. The association between eNOS polymorphisms and ESRD susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CI) in fixed or random effects models. Results: Sixteen articles were identified for the analysis of association between eNOS gene polymorphisms and ESRD risk. A total of 2729 patients and 2190 controls for 4b/a, 851 patients and 1171 controls for G894T, and 513 patients and 487 controls for T786C were included in our analysis. Overall, 4a allele of 4b/a polymorphism produced a significant association in the global population (OR?=?1.47, 95% CI?=?1.05–2.06, p?=?0.03) in a random-effect model; T allele of G894T was also significantly associated with ESRD susceptibility in overall populations (OR?=?2.12, 95% CI?=?1.44–3.12, p?=?0.0001). Furthermore, 4a and T carriers were significantly associated with ESRD risk as well. No association was found between T786C polymorphism and ESRD. Conclusion: The evidence accumulated suggested that 4b/a and G894T polymorphisms in the eNOS gene were associated with ESRD susceptibility, indicating that 4a and T allele carriers might become significant genetic molecular markers for the onset of ESRD in overall populations. However, more studies should be performed in the further studies.     

Klotho Variants and Chronic Hemodialysis Mortality

Patients with end‐stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)‐23 levels correlate with survival in these patients. Klotho is a protein in the vitamin D/FGF‐23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. We therefore hypothesized that genetic variation in the Klotho gene might be associated with survival in subjects with ESRD. We tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n = 1307 white and Asian). We found a significant association between the CC genotype of one tag SNP, rs577912, and increased risk for 1‐yr mortality (RR, 1.76; 95% CI, 1.19–2.59; p = 0.003). This effect was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18–5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16–21% lower Klotho expression compared with the AA/AC genotype. Our data suggest that a specific Klotho variant (rs577912) is linked to survival in ESRD patients initiating chronic hemodialysis and that therapy with activated vitamin D may modify this risk.     

Concomitant presence of endothelial nitric oxide 894T and angiotensin II-converting enzyme D alleles are associated with diabetic nephropathy in a Kurdish population from Western Iran

Aim: The present study investigated the influence of insertion (I)/deletion (D) polymorphism of the angiotensin II‐converting enzyme (ACE) gene in combination with endothelial nitric oxide (eNOS) G894T polymorphism on the predisposition to diabetic nephropathy (DN). Methods: Using polymerase chain reaction (PCR) and PCR‐restriction fragment length polymorphism (PCR‐RFLP) method, the ACE and eNOS polymorphisms were genotyped in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric type 2 diabetes mellitus (T2DM) patients from Western Iran. Results: The presence of eNOS T or ACE D allele was not associated with increased risk of macroalbuminuria (odds ratio (OR) = 1.36, P = 0.27 and OR = 1.6, P = 0.062, respectively). However, in the presence of both alleles there was a trend towards increased risk of macroalbuminuria (fivefold, P = 0.05). Conclusion: Our study indicates that the concomitant presence of both ACE D and eNOS T alleles tends to be associated with an elevation risk of macroalbuminuria compared with the presence of each polymorphism alone. This risk could be attributed to the increasing activity of ACE and angiotensin II level in the presence of D allele and decreasing NO production in the presence of T allele accelerating diabetic nephropathy.     

Risk of bradykinin B2 receptor ‐58T/C gene polymorphism on hypertension: A meta‐analysis

The risk of bradykinin B2 receptor (BDKRB2)‐58T/C gene polymorphism on hypertension remains controversial. The Cochrane Library, Chinese Biomedical Database, EBSCO, Embase, ISI, MEDLINE, and PubMed were retrieved, and relevant articles were selected. The significant association between BDKRB2 ‐58T/C gene polymorphism and risk of hypertension were found under C‐allele comparison (odds ratio (OR): 1.22, 95% confidential intervals (CI): 1.05–1.42), recessive model (OR: 1.32, 95% CI: 1.07–1.64), dominant model (OR: 0.74, 95% CI: 0.58–0.94), homozygote model (OR: 1.66, 95% CI: 1.11–2.47) and heterozygote model (OR: 1.23, 95% CI: 1.06–1.43). The magnitude of the association between the BDKRB2‐58T/C gene polymorphism and risk of hypertension was substantiated in Asians under C‐allele comparison (OR: 1.24, 95% CI: 1.04–1.49), recessive model (OR: 1.39, 95% CI: 1.04–1.86), dominant model (OR: 0.72, 95% CI: 0.56–0.93), homozygote model (OR: 1.78, 95% CI: 1.09–2.90) and heterozygote model (OR: 1.26, 95% CI: 1.07–1.49). No publication bias was found in the meta‐analysis. The meta‐analysis suggested ‐58C allele and ‐58CC genotype increase the risk of hypertension in Asians and African‐Americans. Inversely, ‐58TT genotype decreases the risk of hypertension in Asians and African‐Americans.     

Association between the RAGE gene -374T/A, -429T/C polymorphisms and diabetic nephropathy: a meta-analysis

Abstract

Aim: The investigations into the association between the receptor for advanced glycation end products (RAGE) gene -374T/A, -429T/C polymorphisms and diabetic nephropathy (DN) in several case–control studies have rendered conflicting results. To shed light on these inconclusive findings, a meta-analysis of all the eligible studies relating these two polymorphisms to the risk of DN was conducted. Methods: The databases were searched for relevant articles up to July 2014. A pooled estimate of the genetic association, the heterogeneity between studies, and the publication bias were investigated. Results: Eight studies with 1725 cases and 1857 controls were enrolled in -374T/A polymorphism analysis. The main analysis indicated no association for the allele contrast, the recessive model and the dominant model. Subgroup analyses in Caucasians and in type 2 diabetes also showed no association between -374T/A polymorphism and DN. Five studies with 1019 cases and 792 controls were enrolled in -429T/C polymorphism analysis. The main analysis revealed heterogeneity and no association for the allele contrast and the dominant model. However, the recessive model for -429C allele diminished the heterogeneity and showed a marginal association overall [fixed-effects OR?=?2.83 (1.33–6.00) and random effects OR?=?2.50 (1.00–6.24), respectively]. Conclusions: Our meta-analysis indicated that the RAGE gene -429CC genotype might be a risk factor for DN in patients with type 2 diabetes.     

ACE DD genotype: a predisposing factor for abdominal aortic aneurysm.

OBJECTIVE: To examine the role of polymorphisms in angiotensin converting enzyme (ACE, I/D) and angiotensin II receptor (AT1R, A1166C) in the development of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: We investigated 250 consecutive patients, 217 males and 33 females (median age 72, range 50-83), undergone AAA elective repair and 250 healthy controls, comparable for sex and age. ACE and AT1R polymorphisms were studied by PCR-RFLP analysis. The genotype distribution was in Hardy-Weinberg equilibrium for all polymorphisms. RESULTS: The genotype distribution and allele frequency of ACE I/D, but not AT1R A1166C polymorphism were significantly different between patients and controls (ACE I/D: p=0.0002 and p<0.0001, respectively, and AT1R A1166C: p=0.6 and p=0.4, respectively). An association between the ACE DD genotype and the predisposition to AAA was found (OR DD vs. ID+II=1.9 95% CI 1.3-2.9, p<0.0001). Multivariate analysis adjusted for age, sex, traditional vascular risk factors and other atherosclerotic localizations, showed ACE DD genotype to be independently related to the disease (OR DD vs. ID+II=2.4, 95% CI 1.3-4.2 p=0.003). CONCLUSIONS: Our findings document that ACE DD genotype represents a susceptibility factor for AAA.     

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。     

DD genotype of ACE gene in boys: may it be a risk factor for minimal change nephrotic syndrome?

It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.     

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.