The role of human serum carnosinase-1 in diabetic nephropathy

Shiqi Zhang

    Research output: ThesisThesis fully internal (DIV)

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    Diabetic nephropathy (DN), a renal complication that may occur in diabetic patients, is world-wide the most common cause of end-stage renal failure. Genetic studies have clearly shown that susceptibility to develop DN, is amongst others also determined by the genetic make-up of the diabetic patients. In this scenario, susceptibility to develop DN is caused by variations (also called polymorphisms) in the gene sequence of particular genes. Polymorphisms that are associated with DN are called susceptibility loci or susceptibility genes. Thus far a number of such susceptibility genes for DN have been postulated, one of which is the CNDP1. CNDP1 encodes for the enzyme carnosinase (CN-1) which is mainly produced in the liver and subsequently secreted in the blood. Although currently it is not clear why the CNDP1 is associated with susceptibility to develop DN, it has been shown that individuals that are homozygous for the CNDP1 Mannheim allele have a lower serum CN-1 concentration and a lower risk to develop DN. In the studies presented in the thesis we attempt to better understand the association between DN and the CNDP1 polymorphism with respect to gender (is it stronger in male or female) and tested the hypothesis that serum CN-1 concentrations in type 2 diabetic patients homozygous for the Mannheim allele is different between patients that develop DN and those that do not. In addition both in vitro and in vivo studies have been carried out to delineate the protective role of carnosine in the setting of diabetes.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • Bakker, Stephan, Supervisor
    • Yard, B.A., Supervisor, External person
    • van den Born, Jaap, Co-supervisor
    • Hauske, Sibylle J., Co-supervisor, External person
    Award date11-May-2016
    Place of Publication[Groningen]
    Print ISBNs978-90-367-8636-2
    Electronic ISBNs978-90-367-8635-5
    Publication statusPublished - 2016

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