Associations between endothelial nitric oxide synthase polymorphisms and risk of diabetic nephropathy: an updated meta-analysis

Abstract

Background: Genetic polymorphism of endothelial nitric oxide synthase (eNOS) has been implicated in the risk of diabetic nephropathy (DN), but the published findings were inconsistent. We performed a comprehensive meta-analysis to derive a more precise estimation of the association between genetic polymorphisms of eNOS and the risk of DN. Methods: Six online database were researched on the associations between polymorphisms of eNOS (T786C, G894T, 4b/4a) and DN risk. PRISMA statement and Hardy–Weinberg equilibrium assessment were used in this report. Odds ratio and 95% confidence interval were estimated based on the following genetic contrast/models: allelic model, dominant model, recessive model and co-dominant model. The publication bias and sensitivity analysis were also performed to guarantee the statistical power. Results: A total of 49 case–control studies with 11,990/9754/5131 participants for DN/DM/HC group were eligible for meta-analysis (7/25/31 studies for T786C/G984T/4b/a). For the eNOS-T786C, C allele showed a weak association between C allele and DN risk in DN/T2DM group. For eNOS-G894T, there was an association between T allele and DN risk in the global, Asian and African population in DN/T2DM group. For the eNOS-4b/4a, 4a allele was found contributing significantly to increased DN risk in the global population. Conclusion: Our comprehensive meta-analysis suggests that three polymorphisms of eNOS may be the increased risk factors of DN development, especially in Asian population and T2DM group.     

Association of the T-786C, G894T and 4a/4b polymorphisms of the endothelial nitric oxide synthase gene with vasculogenic erectile dysfunction in Iranian subjects

What's known on the subject? and What does the study add? We know that nitric oxide (NO) plays a significant role in penile tumescence. NO is produced during enzymatic conversion of L‐arginine to L‐citrulline by three distinct isoforms of NO synthase (NOS), namely, inducible (iNOS), endothelial (eNOS) and neural (nNOS). The endothelial isoform of NOS (eNOS), encoded by the NOS3 gene, is the main source of NO. We determined all three eNOS gene polymorphisms in men with vasculogenic erectile dysfunction. There was a significant difference between the group of men with vasculogenic erectile dysfunction and normal healthy men when compared by genotype distribution.

OBJECTIVE

? To investigate the association of the T‐786C, G894T and variable number of tandem repeats (VNTRs) in intron 4 (a/b) polymorphisms of the eNOS gene in Iranian subjects with vasculogenic erectile dysfunction (ED).

PATIENTS AND METHODS

? A total of 322 consecutive patients with vasculogenic ED were recruited. Patients with concomitant risk factors for ED were excluded. ? Patients with ED were identified based on history‐taking, detailed physical examination, serum biochemistry, sex hormone measurements, application of the International Index of Erectile Function (IIEF) questionnaire, and penile duplex Doppler ultrasonography after intracavernosal injection of 20 µg prostaglandin E₁. The control group comprised 318 age‐matched healthy male volunteers. ? Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism and the T‐786C, G894T and VNTR intron 4 polymorphisms of the eNOS gene were determined.

RESULTS

? After multivariate regression analysis, significant differences were seen in the frequencies of genotypes and alleles of the two T‐786C and G894T polymorphisms when patients with ED and normal controls were compared. ? In a multiple logistic regression analysis, the odds ratio (OR) of increased ED was strongly associated with the ‐786C allele [adjusted OR = 3.12, 95% confidence interval (CI) = 2.28–4.25; P= 0.001] and the 894T allele (adjusted OR = 3.87, 95% CI = 2.53–4.87; P= 0.001). ? The data showed a higher prevalence of the T‐786C CC genotype (adjusted OR = 2.72, 95% CI = 1.88–3.65; P= 0.006), and the G894T GT (adjusted OR = 1.72, 95% CI 1.24–2.83; P= 0.037) and G894T TT genotypes (adjusted OR = 3.42, 95% CI 2.42–4.26; P= 0.001) in patients with ED than in the controls.

CONCLUSIONS

? The findings of the present study suggest that the eNOS T‐786C and G894T polymorphisms are strong predictors of the predisposition to ED in addition to traditional risk factors, signifying a genetic influence for this multifactorial disease. ? Further studies in different ethnic populations are needed to better elucidate the role of eNOS gene polymorphism in the pathogenesis of ED.     

Effects of the T-786C,G894T,and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene on the risk of prostate cancer

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 ± 12.4 years) and 340 age-matched healthy controls (mean age 64.9 ± 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) = 3.62, 95% confidence interval (CI): 1.89–7.74, P = 0.002), high grade tumor (OR = 2.46, 95% CI:1.78–4.72; P = 0.006), and advanced disease (OR = 4.67, 95% CI: 2.64?8.61; P = 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b “a” variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR = 2.12, 95% CI: 1.68–3.44; P = 0.031 for 4a/b ab genotype, and OR = 4.32, 95% CI: 2.21–6.08; P = 0.001 for 4a/b aa genotype). In addition, genotypes with the “a” allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR = 4.76, 95% CI: 2.74–8.62; P = 0.001) and advanced CaP (OR = 5.28, 95% CI: 3.64–8.72; P = 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR = 0.44, 95% CI: 0.33–0.77; P = 0.004, and OR = 0.39, 95% CI: 0.26–0.61; P = 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.     

Influence of eNOS gene polymorphisms on carotid atherosclerosis.

INTRODUCTION: Nitric oxide (NO) is an endothelium-derived relaxing factor which plays a role in atherogenetic events. Polymorphisms in the endothelial NO synthase gene (eNOS) influences the functional activity of the enzyme and affect the susceptibility to atherogenesis. In this study we determined whether T-786C, G894T and 4a/4b eNOS genetic variants may increase the susceptibility to carotid atherosclerosis. METHODS: The study groups included 304 consecutive patients with severe carotid stenosis (>/=70%) and 544 control subjects. The eNOS polymorphisms were analysed by molecular biology techniques. RESULTS: The genotype distribution and allele frequency of eNOS 4a/4b, but not T-786C and G894T, polymorphism was significantly different between patients and controls. Using logistic regression with adjustment for other risk factors, the 4a allele and the combined genotype 4a4a+4a4b/894TT+GT and -786CC+TC/894TT+GT were associated with carotid stenosis (OR=1.5, p=0.02; OR=1.8, p=0.01; OR=1.5, p=0.04, respectively). In a subset of patients (30 of 304) with no traditional risk factors for atherosclerosis, a relatively high incidence of the 4a allele and 4a4a+4a4b/-786CC+TC combined genotype was noted. DISCUSSION: Our findings suggest that the 4a allele and the eNOS combined genotypes are independent predisposing factors to carotid atherosclerosis.     

冠心病与内皮型一氧化氮合酶基因多态性的关系

目的 探讨内皮型一氧化氮合酶(eNOS)基因-786T/C,4a4b,894G/T等3个多态性位点与冠心病(CAD)发病相关.方法 对146例中国汉族人群CAD患者和113例正常对照进行遗传学分析,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和PCR技术分析2个SNP位点即-786T/C和894G/T,以及1个VNTR位点4a4b,检测各位点基因型和等位基因频率,采用HaploView 4.0及SPSS 13.0软件经x2检验比较两组间各位点基因型及等位基因频率的差异.结果 CAD组中eNOS基因-786T/C位点CC基因型频率为2.0%,4a4b位点4a/4a基因型频率为5.4%,对照组eNOS基因-786T/C位点CC基因型频率为0.0%,4a4b位点4a/4a基因型频率为0.9%,差异有统计学意义(P＜0.05).CAD组和对照组在eNOS基因的894G/T位点等位基因和基因型频率分布差异均无统计学意义(P＞0.05).结论 eNOS基因-786T/C和4a4b多态性与中国汉族人群CAD存在关联,C等位基因和4a等位基因可能是CAD发病的危险因素.eNOS基因894G/T位点与CAD发病无明显相关.

Abstract：

Objective To investigate the relationship between the 3 polymorphisms ( -786T/C,4a4b,894G/T) in endothelial nitric oxide synthase (eNOS) gene and coronary artery disease (CAD).Methods 146 patients with CAD and 113 healthy unrelated individuals in a Chinese Han nation were involved.The genotype and allele frequency of each polymorphism of the eNOS gene in these patients and normal controls were examined by using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or PCR methods.Genotypes and allele frequency were analyzed by HaploView 4.0 and SPSS13.0 software.Results The frequency of CC genotype of the -786T/C was 2.0%,and that of 4a/4a genotype of the 4a4b was 5.4% in CAD.The frequency of CC genotype of the - 786T/C was 0.0%,and that of 4a/4a genotype of the 4a4b was 0.9% in controls ( P＜0.05 ).There were significant differences in both allele and genotype frequency of -786T/C and 4a4b between CDA group and control group.Between patients with CAD and controls,there were no significant differences in the frequency of the genotypes and alleles of the 894G/T in eNOS gene.Conclusion The - 786T/C and 4a4b polymorphisms of eNOS gene may be associated with CAD.The individuals with C allele of - 786T/C and 4a allele of 4a4b are susceptible to CAD.There is no significant correlation between 894G/T polymorphism in eNOS gene and CAD.     

eNOS G894T polymorphism as a mild predisposing factor for abdominal aortic aneurysm

OBJECTIVE: Abdominal aortic aneurysm (AAA) represents a chronic degenerative condition associated with atherosclerosis. Actually, data from experimental and clinical studies suggest that nitric oxide (NO) is a modulator in maintaining endothelial function and antithrombotic intravascular environment. Reduced vascular NO generation in subjects carrying the rare variants of the eNOS gene might predispose to AAA. No information is available about the influence of the eNOS gene T-786C, G894T, and 4a/4b polymorphisms in the susceptibility to the disease. METHODS: In this study, we evaluated the role of these polymorphisms in the predisposition to AAA and their influence in hypertensive and normotensive patients. We studied 250 consecutive patients with AAA referred to the Unit of Vascular Surgery of the University of Florence compared with 250 truly healthy subjects with a negative history of vascular diseases. All subjects, patients, and controls, underwent duplex scanning examination, and to assess the presence of other atherosclerotic localizations, all patients underwent clinical and instrumental examinations. RESULTS: A significant difference in genotype distribution and allele frequency was observed for eNOS G894T but not for T-786C and 4a/4b polymorphisms. At the multivariate analysis after adjustment for traditional vascular risk factors and other atherosclerotic localizations, the eNOS 894T variant was significantly associated with AAA, according to dominant and recessive models (dominant model odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.21-3.93, P = .007; recessive model OR: 2.7, 95% CI: 1.42-5.20, P = .002). When patients with other atherosclerotic localizations were excluded from the analysis, the 894T variant still remained associated with the predisposition to AAA, according to the models considered (dominant model OR: 2.1, 95%CI: 1.23-3.92, P = .007; recessive model OR: 2.8, 95%CI: 1.45-5.24, P = .002). CONCLUSIONS: The present study showed that the eNOS G894T polymorphism is a mild modulator of the predisposition to AAA apart from traditional risk factors, suggesting a genetic influence on the molecular mechanisms responsible for this complex disease.     

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.     

eNOS gene T786C,G894T and 4a4b polymorphisms and male infertility susceptibility: a meta‐analysis

The association between polymorphism of eNOS and male infertility in several studies was controversial. To explore a more precise estimation of the association, a meta‐analysis of eight case–control studies, including 1,968 cases and 1,539 controls, were selected. The meta‐analysis was conducted by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Overall, the association between T786C and risk of male infertility was obvious (TC vs. TT: OR, 1.20; 95% CI, 1.01–1.42; CC vs. TT: OR, 3.37; 95% CI, 1.65–6.87; TC/CC vs. TT: OR, 1.47; 95% CI, 1.25–1.73; CC vs. TT/TC: OR, 3.18; 95% CI, 1.54–6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27–2.03). However, no overall association was observed between the other two polymorphisms of eNOS (G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility.     

Endothelial nitric oxide synthase polymorphisms are associated with hypertension and cardiovascular disease in renal transplantation

Aim: Nitric oxide (NO), produced by the polymorphic endothelial nitric oxide synthase (NOS3), plays an important role in endothelial function. The aim was to determine the effect of NOS3 polymorphisms on hypertension and cardiovascular disease (CVD) in renal allograft recipients. Methods: Three polymorphisms of NOS3 were examined in 168 renal allograft recipients. A 27 base pair repeat sequence in intron 4 (NOS3 a/b), a single G→T substitution in exon 7 at nucleotide 894 and a T‐786C substitution in the promoter region were studied. Results: Significant differences in the frequencies of the 894T and ?786C alleles between allograft recipients and controls (n = 141) were demonstrated (894T: 40.5% vs 30.1%, P < 0.01; ?786C: 45.2% vs 34.4%, P < 0.01). There was a significant excess of both the 894T and ?786C alleles in hypertensive allograft recipients compared with normotensive allograft recipients and controls (894T: 41.7%, 35.7% and 30.1%, respectively, P < 0.025; ?786C: 47.4%, 37.1% and 34.4%, respectively, P < 0.01), and in allograft recipients with CVD compared with those without CVD and controls (894T: 47.2%, 38.6% and 30.1%, respectively, P < 0.025; ?786C: 54.2%, 42.8% and 34.4%, respectively, P < 0.01). Conclusion: The 894T and ?786C alleles of the NOS3 gene were significantly associated with both hypertension and CVD in renal allograft recipients.     

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     

Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy

Aims: Diabetic nephropathy (DN) is the major cause for end‐stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta‐analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients. Methods: Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta‐analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated. Results: Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11–1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25–2.21, P = 0.0004). In the sub‐group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type‐1. Conclusions: Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.     

The correlation between gene polymorphisms of endothelial nitric oxide synthase and aneurismal subarachnoid hemorrhage

Neurosurgical Review - To discuss the association of the T786C and G894T polymorphisms of endothelial nitric oxide synthase (eNOS) with the occurrence and prognosis of aneurismal subarachnoid...     

Adiponectin gene polymorphisms and susceptibility to diabetic nephropathy: a meta-analysis

Adiponectin (ADIPOQ) plays an important role in the pathogenesis of diabetic nephropathy (DN) and previous studies regarding the association between ADIPOQ polymorphisms and DN risk reported conflicting results. To derive a more precise estimation of this association, we performed a meta-analysis to assess the association between four ADIPOQ polymorphisms [?11391G?>?A (rs17300539), ?11377C?>?G (rs266729), +45T?>?G (rs2241766), and +276G?>?T (rs1501299)] and risk for DN. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association between four aforementioned polymorphisms and susceptibility to DN. Based on the included criteria, we selected 13 articles, among which 7 studies (cases/controls: 2749/7585) for ?11391G?>?A, 8 studies for ?11377C?>?G (3074/3842), 9 studies for +45T?>?G (2654/7710), and 10 studies for +276G?>?T (2812/7821), respectively. Our meta-analysis indicated no evidence heterogeneity among the included studies; thus, the fixed-effects model was used. Overall, there was an association between ADIPOQ ?11391A allele with increased DN risk (OR?=?1.186, 95% CI: 1.051–1.338, p?=?0.006). Subgroup by ethnicity suggested significant association between +45T?>?G polymorphism and DN risk among Caucasians (OR?=?1.122, 95% CI: 1.007–1.250, p?=?0.038). Sensitivity analysis suggested exclusion of any single study did not materially alter the overall pooled ORs above. Future studies are needed to validate these findings.     

Association of endothelial nitric oxide synthase gene intron 4 polymorphism with end-stage renal disease

BACKGROUND: Nitric oxide (NO) released from endothelial cells is related to the maintenance of physiological vascular tone. The impairment of endothelial NO generation brought about by gene polymorphism is considered one of the deterioration factors in progressive renal disease. In the endothelial nitric oxide synthase (eNOS) intron 4 polymorphism, the presence of the aa genotype has been associated with cardiovascular and renal disease. The aim of this study was to investigate the presence of eNOS gene intron 4 polymorphism in patients with end-stage renal disease (ESRD). METHODS: A total of 114 patients and 94 controls were studied. DNA specimens were extracted from blood and amplified by polymerase chain reaction. The alleles were separated by agarose gel electrophoresis. Genotype distribution and allele frequencies were compared between groups using the chi-squared test. RESULTS: Statistical analysis revealed that the frequency of the eNOS4 genotype aa was significantly different in ESRD patients and in controls (P=0.016, OR=2.07, CI 95%: 1.14-3.74). There was also a statistically significant difference between ESRD patients and controls regarding allele carriers (P=0.004; OR=2.26; CI 95%: 1.29-3.96). When the frequencies of allele carriers in the diabetic nephropathy group and in the control group were compared, a significant difference was found (P=0.034, OR=2.28; CI 95%: 1.04-5.00). CONCLUSION: This study showed a strong correlation between eNOS4a polymorphism and end-stage renal disease.     

Association between transforming growth factor-β1gene-509C/T polymorphism and susceptibility of IgA nephropathy: a meta-analysis

A role for transforming growth factor-β₁gene has been suggested in the etiology of IgA nephropathy. However, results have been inconsistent. In this study, a meta-analysis was performed to further clarify the association between transforming growth factor-β₁-509C/T gene polymorphism and the susceptibility of IgA nephropathy. PubMed, EMBASE, Web of Science, CNKI, WanFang, and VIP Data were searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals were calculated using a fixed-effects model or random-effects model. A total of eight publications involving 1355 IgA nephropathy patients and 1464 controls met the inclusion and were analyzed. The pooled ORs for the association between TGF-β₁gene-509C/T polymorphism and IgA nephropathy risk were not statistically significant under all genetic models (for CT+TT vs. CC: OR?=?1.09; 95% CI?=?0.92–1.29, p?=?0.490; for TT vs. CT+CC: OR?=?1.14; 95% CI?=?0.94–1.38, p?=?0.081; for CC vs. TT: OR?=?0.87; 95% CI?=?0.69–1.08, p?=?0.195; for C allele vs. T allele: OR?=?0.92; 95% CI?=?0.83–1.03, p?=?0.149). In the stratified analysis by ethnicity, results also showed no significant association between TGF-β₁ gene-509C/T polymorphism and IgA nephropathy risk in both European and Asian populations. This meta-analysis does not support the hypothesis that TGF-β₁ gene-509C/T polymorphism is a risk factor for the development of IgA nephropathy.     

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

Abstract

The association of transforming growth factor-β1 (TGF-β1) polymorphisms with the risk of chronic kidney diseases (CKD) remains elusive. We aimed to perform a meta-analysis to evaluate the relationship between TGF-β1 polymorphisms and the susceptibility to CKD. Association studies were searched according to a defined criteria using electronic databases. The strength of association between TGF-β1 polymorphisms and CKD risk was evaluated by odds ratio (OR) with the corresponding 95% confidence interval (CI). Nine case–control studies were identified. T allele at the +869 T/C polymorphism was associated with a lower risk of CKD in Asians (p?=?0.003). TT genotype at the +869 T/C polymorphism was associated with a lower risk of CKD in overall populations and Asians (p?=?0.007 and <10^?4, respectively). CC genotype at the +869 T/C polymorphism was associated with the risk of CKD in Asians (p?=?0.002). T allele at the ?509 T/C polymorphism was associated with the risk of CKD in overall populations and Asians (p?=?0.044 and 0.050, respectively). TT genotype at the ?509 T/C polymorphism was associated with CKD risk in overall populations, Caucasians and Asians (p?<?10^?4, <10^?4, and <10^?4, respectively). No evidence of significant publication bias was noted. In conclusion, T allele at the +869 T/C polymorphism may be a protective factor against CKD risk in Asians. TT genotype at the +869 T/C polymorphism may be an indicator of lower risk of CKD in overall populations and Asians. CC genotype at the +869 T/C polymorphism may predict the susceptibility to CKD in Asians. T allele at the ?509 T/C polymorphism may be an indicator of CKD risk in overall populations and Asians. TT genotype at the ?509 T/C polymorphism was a risk factor for CKD onset in overall populations, Caucasians and Asians.     

Manganese superoxide dismutase,glutathione peroxidase and catalase gene polymorphisms and clinical outcomes in acute kidney injury

Introduction The aim of this study was to evaluate the potential association of single gene polymorphisms of manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1) and catalase (CAT) with clinical outcomes of acute kidney injury (AKI). Materials and methods Ninety AKI patients and 101 healthy volunteers were included in the study. Determination of MnSOD rs4880, GPX1 rs1050450 and CAT rs769217 polymorphisms was performed using real-time polymerase chain reaction amplification. The duration of hospitalization of AKI patients, dialysis and intensive care requirements, sepsis, oliguria and in-hospital mortality rates were assessed. Results The MnSOD, GPX1 and CAT genotypes and allele frequencies of AKI patients did not differ significantly from those of healthy controls. In patients with a T allele in the ninth exon of the CAT gene, intensive care requirements were greater than those of patients with the CC genotype (p?=?0.04). In addition, sepsis and in-hospital mortality were observed significantly more frequently in patients with a T allele in the ninth exon of the CAT gene (p?=?0.03). Logistic regression analysis determined that bearing a T allele was the primary determinant of intensive care requirements and in-hospital mortality, independent of patient age, gender, presence of diabetes and dialysis requirements (OR 6.10, 95% CI 1.34–27.81, p?=?0.02 and OR 10.25, 95% CI 1.13–92.80, p?=?0.04, respectively). Conclusion Among AKI patients in the Turkish population, hospital morbidity and mortality were found to be more frequent in patients bearing a T allele of the rs769217 polymorphism of the CAT gene.     

4 G/4 G polymorphism of plasminogen activator inhibitor-1 gene increases the risk of diabetic nephropathy

Diabetic nephropathy (DN) has become the most common pathogenesis of end-stage renal disease. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of DN. A meta-analysis was conducted to investigate the association between 4?G/5?G variants in the PAI-1 gene and DN susceptibility. Databases including Pubmed, EMBASE, ISI, etc., were searched to find relevant studies. Odds ratios (ORs) with 95% con?dence intervals (CIs) were used to evaluate the strength of associations. Ten studies involving 1366 cases and 1888 controls were included. Significant association between 4?G/4?G variant and DN risk was observed (OR 1.26, 95% CI 1.08–1.48, p?=?0.004) in overall populations by the recessive model. 4?G allele was also associated with the risk of DN than the 5?G allele (OR 1.15, 95% CI 1.04–1.27, p?=?0.008). In the subgroup analysis performed by the ethnicity, 4?G/4?G polymorphism was significantly associated with DN risk than 4?G/5?G?+?5?G/5?G in East Asians (OR 1.42, 95% CI 1.03–1.96; p?=?0.03), but not in Caucasians. In the strati?ed analysis by types of DM, the results showed significant association between 4?G/4?G variant and DN in Type-2 DM (OR 1.42, 95% CI 1.03–1.96, p?=?0.03). In conclusion, 4?G/4?G phenotype of PAI-1 gene may be associated with DN risk. Additional larger studies should be conducted in future analyses.     

Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population

Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED.     

Association of Megsin 2093C/T, 2180C/T and C25663G gene polymorphism with the risk of IgA nephropathy

The association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms and IgA nephropathy (IgAN) risk remains unclear. We aimed to evaluate the association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms and IgAN risk by performing a meta-analysis. Eligible studies were searched according to predefined criteria by using electronic databases. Six articles were identified for the analysis of the association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms and IgAN risk. 2093C/T C allele was associated with IgAN risk in overall populations and Asians (overall populations: p?=?0.014, Asians: p?=?0.037). 2093C/T CC/TT genotype was not associated with IgAN risk in overall populations, Caucasians and Asians. 2180C/T C allele was correlated with IgAN risk in Caucasians (p?=?0.024). 2180C/T CC/TT genotype was not associated with IgAN risk in overall populations, Caucasians and Asians. C25663G gene polymorphism was not associated with IgAN onset in Asians. In conclusion, megsin 2093C/T C allele may be genetic marker for IgAN susceptibility in overall populations and Asians. 2180C/T C allele may be risk factor for IgAN onset in Caucasians. However, more studies should be performed in the future.