The genetics of vascular complications in autosomal dominant poly-cystic kidney disease (adpkd)

Sandro Rossetti, Peter C Harris

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The most important extra-renal manifestation of autosomal dominant polycystic kidney disease (ADPKD) in terms of debilitating injury and premature death is the development of intracranial aneurysms (IAs) and other vascular complications, resulting in subarachnoid hemorrhage (SAH). IAs are found at a rate approximately five times higher in ADPKD patients than in the general population and in patients with a family history of SAH/IAs the frequency is elevated further three to five times, indicating the importance of genetic factors in its etiology. Expression of the ADPKD gene products, polycystin-1 (PKD1) and polycystin-2 (PKD2), in vascular smooth muscle and the endothelium, and evidence that reduced levels of these proteins leads to IA development in mouse models, suggests a direct role of these proteins in the vascular disease. PKD1 and PKD2 patients seem equally likely to develop IAs, while patients with mutations to the 5' half of PKD1 may more likely have vascular complications. Genome wide association and candidate studies of multiplex families with IAs without ADPKD have identified a number of genes/proteins that may be risk factors for the development of IAs. These candidate proteins largely have roles in the maintenance and remodeling of the arterial wall of small brain arteries. The development of the genetic methodologies of massively parallel sequencing mean it is now possible to test these and other candidates in ADPKD families with multiplex and singleton IA cases. Identifying strong modifiers of this phenotype will be important for prioritizing patients for presymptomatic screening and interventions.

Original languageEnglish (US)
Pages (from-to)37-43
Number of pages7
JournalCurrent Hypertension Reviews
Volume9
Issue number1
StatePublished - 2013

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Cystic Kidney Diseases
Intracranial Aneurysm
Blood Vessels
Autosomal Dominant Polycystic Kidney
Subarachnoid Hemorrhage
Proteins
High-Throughput Nucleotide Sequencing
Premature Mortality
Genome-Wide Association Study
Vascular Diseases
Vascular Smooth Muscle
Endothelium
Arteries
Maintenance
Phenotype
Kidney
Mutation
Wounds and Injuries
Brain

Keywords

  • Adpkd
  • Genetic modifiers
  • Genotype/phenotype correlations
  • Intracranial aneurysms

ASJC Scopus subject areas

  • Internal Medicine

Cite this

The genetics of vascular complications in autosomal dominant poly-cystic kidney disease (adpkd). / Rossetti, Sandro; Harris, Peter C.

In: Current Hypertension Reviews, Vol. 9, No. 1, 2013, p. 37-43.

Research output: Contribution to journalArticle

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