Dataset Information

Renalase gene polymorphisms in patients with type 2 diabetes, hypertension and stroke.

ABSTRACT: Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study was to investigate the involvement of renalase gene polymorphisms in hypertension in type 2 diabetes patients. A total of 892 patients and 400 controls were genotyped with three SNPs in the renalase gene. The C allele of rs2296545 SNP was associated with hypertension (P < 0.01). For rs2576178 SNP, frequencies in hypertensive patients differed from controls, but not from normotensive patients. For rs10887800 SNP, the differences in the G allele frequencies were observed in hypertensive patients with stroke, with 66% of patients being GG homozygotes. To confirm observed association we later genotyped 130 stroke patients without diabetes. The OR for risk allele was 1.79 (95% CI 1.33-2.41). In conclusion, the renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result is a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. The G allele of this polymorphism might thus be useful in identifying diabetes patients at increased risk of stroke.

SUBMITTER: Buraczynska M

PROVIDER: S-EPMC3220827 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Renalase gene polymorphisms in patients with type 2 diabetes, hypertension and stroke.

Buraczynska Monika M Zukowski Pawel P Buraczynska Kinga K Mozul Slawomir S Ksiazek Andrzej A

Neuromolecular medicine 20111002 4

Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study was to investigate the involvement of renalase gene polymorphisms in hypertension in type 2 diabetes patients. A total of 892 patients and 400 controls were genotyped with three SNPs ...[more]

PMID: 21964580

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Project description:BackgroundDysregulations of AQP7 and AQP9 were found to be related to lipid metabolism abnormality, which had been proven to be one of the mechanisms of stroke. However, limited epidemiological studies explore the associations between AQP7 and AQP9 and the risk of stroke among patients with hypertension in China.AimsWe aimed to investigate the associations between genetic variants in AQP7 and AQP9 and the risk of stroke among patients with hypertension, as well as to explore gene-gene and gene-environment interactions.MethodsBaseline blood samples were drawn from 211 cases with stroke and 633 matched controls. Genomic DNA was extracted by a commercially available kit. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs2542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes.ResultsParticipants with the rs2989924 GG genotype were found to be with a 1.74-fold increased risk of stroke compared to those with the AA+AG genotype, and this association remained significant after adjustment for potential confounders (odds ratio (OR): 1.74, 95% confidence interval (CI): 1.23-2.46). The SNP rs3758269 CC+TT genotype was found to be with a 33% decreased risk of stroke after multivariate adjustment (OR: 0.67, 95% CI: 0.45-0.99) compared to the rs3758269 CC genotype. The significantly increased risk of stroke was prominent among males, patients aged 60 or above, and participants who were overweight and with a harbored genetic variant in SNP rs2989924. After adjusting potential confounders, the SNP rs3758269 CT+TT genotype was found to be significantly associated with a decreased risk of stroke compared to the CC genotype among participants younger than 60 years old or overweight. No statistically significant associations were observed between genotypes of rs2542743, rs57139208, or rs16939881 with the risk of stroke. Neither interactions nor linkage disequilibrium had been observed in this study.ConclusionsThis study suggests that SNPs rs2989924 and rs3758269 are associated with the risk of stroke among patients with hypertension, while there were no statistically significant associations between rs2542743, rs57139208, and rs16939881 and the risk of stroke being observed.

Project description:AIM:To investigate the association between a set of six candidate genes and the risk of diabetic retinopathy (DR) in an urban community cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS:A population-based cross-sectional study. The diabetic subjects were recruited from an urban community in Beijing and categorized into groups of proliferative diabetic retinopathy (PDR), non-proliferative diabetic retinopathy (NPDR), or diabetic without any retinopathy (DWR) based on the fundus photography and duration of diabetes. Six candidate genes, including advanced glycation end product specific receptor (AGER), aldose reductase (AKR1B1), inducible nitric oxide synthase (iNOS), pigment epithelium derived factor (PEDF), tumor necrosis factor-alpha (TNF-α), and paraoxonase 1 (PON1), were chosen based on Meta-analysis of genetic association studies for DR and biochemical pathways implicated in DR progression. The allele and genotype distribution of 21 functional single-nucleotide polymorphisms (SNPs) in those 6 candidate genes were investigated using MassARRAY genotyping system. RESULTS:Among 1461 diabetic patients recruited from community, 569 were selected in following genotyping analysis, including 97 patients with PDR, 217 with NPDR, and 255 with DWR. For the promoter variant rs1051993 in AGER gene, the distribution of allele and genotype in PDR group differed from that in DWR group (allele: P=0.011; genotype: P=0.01). Compared with DWR, patients with PDR had lower frequencies of heterozygous genotype GT (9.8% for DWR, 1% for PDR, OR: 0.10, 95%CI: 0.01-0.72) and minor allele T (4.9% for DWR, 0.5% for PDR, OR: 0.10, 95%CI: 0.01-0.75). In multivariate model, the distribution of genotype for rs1051993 in PDR group was significantly different from that in DWR group (GT vs GG: OR: 0.07, 95%CI: 0.01-0.61, P<0.001). No association with DR was observed in other genotyped SNPs. CONCLUSION:The data suggest a significant association of the promoter variant rs1051993 in AGER gene with PDR in Chinese cohort with T2DM.

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Renalase gene polymorphisms in patients with type 2 diabetes, hypertension and stroke.

Publications

Renalase gene polymorphisms in patients with type 2 diabetes, hypertension and stroke.

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