Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus
| العنوان: | Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus |
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| المؤلفون: | Alexander P. Maxwell, Vardhman K. Rakyan, David A. Savage, Christopher G. Bell, Stephan Beck, Andrew E. Teschendorff |
| المصدر: | Bell, C G, Teschendorff, A E, Rakyan, V K, Maxwell, A P, Beck, S & Savage, D A 2010, ' Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus ', BMC Medical Genomics, vol. 3, 33 . https://doi.org/10.1186/1755-8794-3-33Test BMC Medical Genomics BMC Medical Genomics, Vol 3, Iss 1, p 33 (2010) |
| بيانات النشر: | Springer Nature |
| مصطلحات موضوعية: | Adult, Male, lcsh:Internal medicine, lcsh:QH426-470, endocrine system diseases, Nerve Tissue Proteins, Bioinformatics, Nephropathy, Diabetic nephropathy, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Genetics, Humans, Diabetic Nephropathies, Genetic Predisposition to Disease, Genetics(clinical), lcsh:RC31-1245, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Type 1 diabetes, business.industry, Genome, Human, Case-control study, nutritional and metabolic diseases, Epigenome, DNA Methylation, Middle Aged, medicine.disease, 3. Good health, lcsh:Genetics, Diabetes Mellitus, Type 1, Case-Control Studies, CpG Islands, Female, Transcription Initiation Site, business, 030217 neurology & neurosurgery, Epigenetics of diabetes Type 2, Kidney disease, Research Article |
| الوصف: | Background Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. Methods We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium® HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. Results Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. Conclusion This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy. |
| وصف الملف: | application/pdf; text |
| اللغة: | English |
| تدمد: | 1755-8794 |
| DOI: | 10.1186/1755-8794-3-33 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a4c09718aee2772455ac4556e55e7f7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6a4c09718aee2772455ac4556e55e7f7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17558794 |
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| DOI: | 10.1186/1755-8794-3-33 |