Association of ecNOS gene polymorphisms with end stage renal diseases

Nagase, Sohji; Suzuki, Hiromichi; Wang, Ying; Kikuchi, Shuichi; Hirayama, Aki; Ueda, Atsushi; Takada, Kenji; Oteki, Takaaki; Obara, Masahiko; Aoyagi, Kazumasa; Kôyama, Akio

doi:10.1007/978-1-4615-0247-0_16

Cited by 38 publications

(50 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2-6,13,38 -51 Two articles involved only patients with microalbuminuria, and therefore these articles were excluded. 52,53 The genotype distribution of one study 54 was identical with the one in Nagase et al, 44 and in one study, 55 the subjects overlapped with the subjects of the study by Buraczynska et al 43 Figure 1 presents a flowchart of retrieved studies and studies excluded, with specification of reasons. The studies were published between 1999 and 2008.…”

Section: Eligible Studies and Study Characteristicsmentioning

confidence: 75%

See 1 more Smart Citation

Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: A HuGE review and meta-analysis

Ζιντζαράς

Papathanasiou

Stefanidis

2009

Genetics in Medicine

View full text Add to dashboard Cite

Candidate-gene association studies that examined the association between polymorphisms of endothelial nitric oxide synthase (NOS3) gene (G894T, 4b/a, and T786C) and diabetic nephropathy or diabetes leading to severe nephropathy produced inconclusive results. Thus, a meta-analysis of all candidate-gene association studies with endothelial nitric oxide synthase genotyping (7401 cases and 8046 controls) was conducted. Other study designs, such as family-based association studies and genome-wide linkage and association studies were also reviewed for supportive evidence of implication of endothelial nitric oxide synthase gene in diabetic nephropathy. The meta-analysis showed that G894T is significantly associated with diabetic nephropathy and diabetes leading to severe nephropathy in type 2 diabetics and in East Asians, respectively. Concerning the 4b/a polymorphism and its relationship to diabetes leading to severe nephropathy, a significant association was shown for East Asians. Heterogeneity between studies was in general high. There was no differential magnitude of effect in large versus small studies. One genome-wide linkage scan provided evidence of linkage nearby the endothelial nitric oxide synthase locus. Studies exploring gene and environment interactions with endothelial nitric oxide synthase polymorphisms may help understand better the genetics of diabetic nephropathy. Genet Key Words: eNOS, NOS3, G894T, 4b/a, T786C, diabetic nephropathy, diabetes, polymorphism, meta-analysis, genetic epidemiology Gene and gene variantsVascular endothelial nitric oxide (NO) regulates endothelial function and precipitates vasodilatory effects in multiple organs, including the kidney. 1 NO is produced by the oxidation of L-arginine to L-citrulline by NO synthase (NOS). There are three isoforms of NOS: endothelial NOS (eNOS), neuronal NOS, and inducible NOS. 2,3 Each isoform is coded by separate genes with a different pattern of expression. 4 The eNOS gene (NOS3) is located on chromosome 7q35-36, and it comprises 26 exons and 25 introns, with an entire length of 21kb. 4 Variants of eNOS gene contribute to endothelial dysfunction and attenuate the NO production. 5 Dysfunctional eNOS may play a critical role in the pathogenetic pathway, leading to diabetic vascular complications including diabetic nephropathy (DN). 6 Several polymorphisms of the eNOS gene have been identified, and their association with various diseases has been investigated, including coronary artery disease, myocardial infarction, coronary spasm, hypertension, end-stage renal disease (ESRD), and DN. 4,[7][8][9][10] The most clinically relevant polymorphisms that have been described in the eNOS gene 11 are the following: (i) a G894T substitution in exon 7 that results in a Glu to Asp substitution at codon 298, 7 (ii) an insertion-deletion in intron 4 consisting of two alleles (the a-deletion has 4 tandem 27-bp repeats, and the b-insertion has 5 repeats), 12 and (iii) a T786C substitution in the promoter region, which is strongly linked to 4b/a....

show abstract

Section: Eligible Studies and Study Characteristicsmentioning

confidence: 75%

“…In one study, 44 the distribution of the genotypes in control group was not in HWE (P Ͻ 0.05), indicating genotyping errors and/or population stratification 25 ; therefore, a sensitivity analysis was performed excluding this study. Three studies provided analyses of eNOS haplotypes.…”

Section: Summary Statisticsmentioning

confidence: 99%

Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: A HuGE review and meta-analysis

Ζιντζαράς

Papathanasiou

Stefanidis

2009

Genetics in Medicine

View full text Add to dashboard Cite

show abstract

“…In 2003, Nagase et al showed that some intronic polymorphisms in eNOS may change its transcriptional activity. They also found that some exonic polymorphisms may alter the three-dimensional structure of the enzyme and affect the progression of renal disease via decreased NO synthesis [78]. In a meta-analysis of 18 eNOS studies, the eNOS4b/a polymorphism was significantly associated with an overall increased risk of DKD across all Legend: * After combined meta-analysis (meta-analysis results for GENIE discovery cohorts + meta-analysis results for independent replication cohorts), these signals reached genome-wide significance in the analysis.…”

Section: Candidate Gene Association Studiesmentioning

confidence: 99%

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

Davoudi¹,

Sobrin²

2016

Rev Diabet Stud

View full text Add to dashboard Cite

■ AbstractBoth type 1 and type 2 diabetes mellitus can lead to the common microvascular complications of diabetic retinopathy, kidney disease, and neuropathy. Diabetic patients do not universally develop these complications. Long duration of diabetes and poor glycemic control explain a lot of the variability in the development of microvascular complications, but not all. Genetic factors account for some of the remaining variability because of the heritability and familial clustering of these complications. There have been a large number of investigations, including linkage studies, candidate gene studies, and genome-wide association studies, all of which have sought to identify the specific variants that increase susceptibility. For retinopathy, several genomewide association studies have been performed in small or midsize samples, but no reproducible loci across the studies have been identified. For diabetic kidney disease, genomewide association studies in larger samples have been performed, and loci for this complication are beginning to emerge. However, validation of the existing discoveries, and further novel discoveries in larger samples is ongoing. The amount of genetic research into diabetic neuropathy has been very limited, and much is dedicated to the understanding of genetic risk factors only. Collaborations that pool samples and aim to detect phenotype classifications more precisely are promising avenues for a better explanation of the genetics of diabetic microvascular complications.

show abstract

“…According to the inclusion and exclusion criteria, six articles [17][18][19][20][21][22] were identified for the analysis of the association between eNOS Glu298Asp gene polymorphism and ESRD susceptibility in our review ( Figure 1). Two studies 17,21 were conducted in Caucasians, two investigations 18,19 for Asians, one 22 in Africans, and one 20 in Brazil population. The data of our interest were extracted and shown in Table 1.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…One study 18 from Asians that the genotype distributions in the controls were significantly deviated from HWE was excluded from our sensitive analysis. Furthermore, one study 22 from Africans had not provided the detailed gene distribution data for the control group for the HWE test and it was excluded from the sensitive analysis.…”

Section: Sensitivity Analysismentioning

confidence: 99%

Association of Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism with the Risk of End-Stage Renal Disease

Zhou

Yin

2013

Renal Failure

View full text Add to dashboard Cite

The association between endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphism and end-stage renal disease (ESRD) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS Glu298Asp gene polymorphism and ESRD susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Six articles were identified for the analysis of association between eNOS Glu298Asp gene polymorphism and ESRD risk. T allele was associated with ESRD susceptibility in overall populations and in Asians (overall populations: p ¼ 0.01, Asian: p < 0.00001). Furthermore, GG genotype might play a protective role against ESRD onset for overall populations, Asians, and Africans. However, a link between eNOS Glu298Asp gene polymorphism and ESRD risk was not found in Caucasians and Brazil population. In conclusion, T allele might become a significant genetic molecular marker for the onset of ESRD in overall populations, and in Asians. However, more studies should be performed in the future.

show abstract

Association of ecNOS gene polymorphisms with end stage renal diseases

Cited by 38 publications

References 25 publications

Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: A HuGE review and meta-analysis

Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: A HuGE review and meta-analysis

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

Association of Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism with the Risk of End-Stage Renal Disease

Contact Info

Product

Resources

About