PhD ceremony: Ms. A. Reznichenko, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Translational renal genetics
Promotor(s): prof. G.J. Navis, prof. H. Snieder
Faculty: Medical Sciences
Chronic kidney disease (CKD) is a significant and increasing global challenge for public health. It affects approximately 10% of the general population in industrialized nations. Identification of the genetic variants involved in the susceptibility and progression of CKD will improve our understanding of biological mechanisms underlying renal function and will ultimately lead to the development of novel tools for diagnosis, prediction, prevention and treatment. The studies described in this thesis aimed at carrying the genotype-phenotype associations observed in prior genome-wide association studies (GWAS) on renal traits towards the realm of clinical nephrology. To translate GWAS findings to renal pathophysiology, we selected loci with biological plausibility based on prior knowledge of the function of gene in renal (patho)physiology, i.e., UMOD, coding for uromodulin, the most abundant protein in urine; CUBN, coding for cubilin, which plays a role in protein re-absorption in proximal tubule; and SLC22A2, coding for a tubular transporter involved in creatinine secretion. In summary, the results illustrate the relevance of dedicated clinical studies for the translation of genotype-phenotype associations from GWAS to the setting of clinical nephrology. Our data showed that refinement and dissection of the renal phenotype allow better insight into the functional and clinical consequences of the genetic variant. These new insights will eventually contribute to elucidation of the genetic basis of susceptibility and progression of CKD and support the development of novel tools for diagnosis, prevention, prediction and treatment, to translate, all in all, into benefit for the renal patient.
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