Tamm-Horsfall protein gene is associated with distal tubular dysfunction in patients with type 1 diabetes
(2010) In Scandinavian Journal of Urology and Nephrology 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1752038
- author
- Mollsten, Anna and Torffvit, Ole LU
- organization
- publishing date
- 2010
- 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 Nephrology
- volume
- 44
- issue
- 6
- pages
- 438 - 444
- publisher
- Taylor & Francis
- external identifiers
-
- wos:000284316200011
- scopus:78649268736
- pmid:20624112
- 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
- 2016-04-01 14:37:26
- date last changed
- 2022-03-29 21:57:45
@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}},
keywords = {{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 Nephrology}},
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}},
doi = {{10.3109/00365599.2010.504190}},
volume = {{44}},
year = {{2010}},
}