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Tamm-Horsfall protein gene is associated with distal tubular dysfunction in patients with type 1 diabetes

Mollsten, Anna and Torffvit, Ole LU (2010) In Scandinavian Journal of Urology and Nephrology1967-01-01+01:002013-01-01+01:00 44(6). p.438-444
Abstract
Objective. The first changes in the diabetic kidney are glycogen deposits in the epithelial cells of the thick ascending limb of Henle, which leads to decreased production of Tamm-Horsfall protein (THP). The production of THP is also influenced by nitric oxide (NO). The aims of this study were to investigate whether low excretion of THP, a sign of distal tubular dysfunction, in patients with type 1 diabetes was associated with polymorphisms in the THP gene and the endothelial NO synthase (eNOS) gene. Material and methods. Urine was collected from 301 patients with type 1 diabetes, 164 with normoalbuminuria, 91 with microalbuminuria and 46 with macroalbuminuria. Urinary THP concentration below median (3.12 mg/l) was defined as tubular... (More)
Objective. The first changes in the diabetic kidney are glycogen deposits in the epithelial cells of the thick ascending limb of Henle, which leads to decreased production of Tamm-Horsfall protein (THP). The production of THP is also influenced by nitric oxide (NO). The aims of this study were to investigate whether low excretion of THP, a sign of distal tubular dysfunction, in patients with type 1 diabetes was associated with polymorphisms in the THP gene and the endothelial NO synthase (eNOS) gene. Material and methods. Urine was collected from 301 patients with type 1 diabetes, 164 with normoalbuminuria, 91 with microalbuminuria and 46 with macroalbuminuria. Urinary THP concentration below median (3.12 mg/l) was defined as tubular dysfunction. Representative polymorphisms were analysed in the THP and eNOS genes. Results. Patients with tubular dysfunction had longer diabetes duration and higher blood pressure than patients without tubular dysfunction. Tubular dysfunction was common in patients with macroalbuminuria (70% of patients) and it was associated with the AA+AT genotypes of rs12444268 in the THP gene [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.1-2.8], and the GG genotype of rs1799983 in the eNOS gene (OR 1.6, 95% CI 1.03-2.6). When adjusting for other associated factors, diabetes duration, glycosylated haemoglobin (HbA(1c)), mean arterial pressure and albuminuria, the THP rs12444268 and macroalbuminuria were independently associated with tubular dysfunction. Conclusion. Distal tubular dysfunction was associated with the THP gene and macroalbuminuria in patients with type 1 diabetes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
tubular dysfunction, Tamm-Horsfall protein, eNOS gene, Albuminuria, diabetic nephropathy, UMOD gene
in
Scandinavian Journal of Urology and Nephrology1967-01-01+01:002013-01-01+01:00
volume
44
issue
6
pages
438 - 444
publisher
Taylor & Francis
external identifiers
  • wos:000284316200011
  • scopus:78649268736
ISSN
0036-5599
DOI
10.3109/00365599.2010.504190
language
English
LU publication?
yes
id
f4879273-ea4d-4a73-86ca-e8a05b1391fc (old id 1752038)
date added to LUP
2011-01-04 08:02:33
date last changed
2018-06-24 04:23:25
@article{f4879273-ea4d-4a73-86ca-e8a05b1391fc,
  abstract     = {Objective. The first changes in the diabetic kidney are glycogen deposits in the epithelial cells of the thick ascending limb of Henle, which leads to decreased production of Tamm-Horsfall protein (THP). The production of THP is also influenced by nitric oxide (NO). The aims of this study were to investigate whether low excretion of THP, a sign of distal tubular dysfunction, in patients with type 1 diabetes was associated with polymorphisms in the THP gene and the endothelial NO synthase (eNOS) gene. Material and methods. Urine was collected from 301 patients with type 1 diabetes, 164 with normoalbuminuria, 91 with microalbuminuria and 46 with macroalbuminuria. Urinary THP concentration below median (3.12 mg/l) was defined as tubular dysfunction. Representative polymorphisms were analysed in the THP and eNOS genes. Results. Patients with tubular dysfunction had longer diabetes duration and higher blood pressure than patients without tubular dysfunction. Tubular dysfunction was common in patients with macroalbuminuria (70% of patients) and it was associated with the AA+AT genotypes of rs12444268 in the THP gene [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.1-2.8], and the GG genotype of rs1799983 in the eNOS gene (OR 1.6, 95% CI 1.03-2.6). When adjusting for other associated factors, diabetes duration, glycosylated haemoglobin (HbA(1c)), mean arterial pressure and albuminuria, the THP rs12444268 and macroalbuminuria were independently associated with tubular dysfunction. Conclusion. Distal tubular dysfunction was associated with the THP gene and macroalbuminuria in patients with type 1 diabetes.},
  author       = {Mollsten, Anna and Torffvit, Ole},
  issn         = {0036-5599},
  keyword      = {tubular dysfunction,Tamm-Horsfall protein,eNOS gene,Albuminuria,diabetic nephropathy,UMOD gene},
  language     = {eng},
  number       = {6},
  pages        = {438--444},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Urology and Nephrology1967-01-01+01:002013-01-01+01:00},
  title        = {Tamm-Horsfall protein gene is associated with distal tubular dysfunction in patients with type 1 diabetes},
  url          = {http://dx.doi.org/10.3109/00365599.2010.504190},
  volume       = {44},
  year         = {2010},
}