Association analysis of Notch pathway signalling genes in diabetic nephropathy
| العنوان: | Association analysis of Notch pathway signalling genes in diabetic nephropathy |
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| المؤلفون: | Alexander P. Maxwell, Christopher Patterson, David A. Savage, Dominic Kavanagh, Gareth J. McKay, Amy Jayne McKnight |
| المصدر: | Diabetologia. 54:334-338 |
| بيانات النشر: | Springer Science and Business Media LLC, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Male, Oncology, medicine.medical_specialty, JAG1, Epithelial-Mesenchymal Transition, Adolescent, Genotype, Endocrinology, Diabetes and Metabolism, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Nephropathy, Diabetic nephropathy, ADAM10 Protein, Young Adult, Diabetes mellitus, Internal medicine, Basic Helix-Loop-Helix Transcription Factors, Internal Medicine, medicine, Humans, Diabetic Nephropathies, Genetic Predisposition to Disease, Serrate-Jagged Proteins, Child, Receptor, Notch3, Genetic association, Homeodomain Proteins, Type 1 diabetes, Receptors, Notch, business.industry, Calcium-Binding Proteins, Haplotype, Membrane Proteins, medicine.disease, ADAM Proteins, Diabetes Mellitus, Type 1, Immunology, Intercellular Signaling Peptides and Proteins, Transcription Factor HES-1, Female, Amyloid Precursor Protein Secretases, business, Jagged-1 Protein, Signal Transduction |
| الوصف: | Several studies have provided compelling evidence implicating the Notch signalling pathway in diabetic nephropathy. Co-regulation of Notch signalling pathway genes with GREM1 has recently been demonstrated and several genes involved in the Notch pathway are differentially expressed in kidney biopsies from individuals with diabetic nephropathy. We assessed single-nucleotide polymorphisms (SNPs; n = 42) in four of these key genes (JAG1, HES1, NOTCH3 and ADAM10) for association with diabetic nephropathy using a case–control design. Tag SNPs and potentially functional SNPs were genotyped using Sequenom or Taqman technologies in a total of 1371 individuals with type 1 diabetes (668 patients with nephropathy and 703 controls without nephropathy). Patients and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK ( http://pngu.mgh.harvard.eduTest/∼purcell/plink/ ) and haplotype frequencies in patients and controls were compared. Adjustment for multiple testing was performed by permutation testing. In analyses stratified by centre, we identified six SNPs, rs8708 and rs11699674 (JAG1), rs10423702 and rs1548555 (NOTCH3), rs2054096 and rs8027998 (ADAM10) as being associated with diabetic nephropathy before, but not after, adjustment for multiple testing. Haplotype and subgroup analysis according to duration of diabetes also failed to find an association with diabetic nephropathy. Our results suggest that common variants in JAG1, HES1, NOTCH3 and ADAM10 are not strongly associated with diabetic nephropathy in type 1 diabetes among white individuals. Our findings, however, cannot entirely exclude these genes from involvement in the pathogenesis of diabetic nephropathy. |
| تدمد: | 1432-0428 0012-186X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b75118c33705f9427927addffb317790Test https://doi.org/10.1007/s00125-010-1978-3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b75118c33705f9427927addffb317790 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X |
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