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

Scandinavian Journal of Urology and Nephrology
Anna Möllsten, O Torffvit

Abstract

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. 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. 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 othe...Continue Reading

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Citations

Apr 16, 2015·PloS One·Katja PetzoldLaura Rotar
Jan 25, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tsai-Hung WuChang-Youh Tsai
Dec 20, 2015·Clinical Journal of the American Society of Nephrology : CJASN·Anthony J Bleyer, Stanislav Kmoch
Feb 10, 2017·Journal of Diabetes Research·Neng-Jun LouAi-Li Sun
Jun 7, 2019·Current Diabetes Reports·Olanrewaju A OlaoyeMichelle L Gumz

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