title: Use of single-nucleotide polymorphisms in the search for genetic modifiers of the uremic phenotype.
abstract: As the modern nephrology community continues to be burdened with growing numbers of patients with end-stage renal disease (ESRD) and exceptionally high mortality rates, it is obvious that progress in the development of preventive and therapeutic strategies has not been sufficient. This urges nephrologists to focus on the underlying mechanisms for ESRD morbidity and mortality, and in particular on cardiovascular disease (CVD), which is the major contributor to premature death in this patient group. The high prevalence of inflammation, vascular ossification, and oxidative stress in ESRD predisposes these patients to CVD. Because genetic risk factors may modulate the pathophysiologic response, genotype-phenotype association studies may provide ways of predicting individual disease progression and may shed some light on key regulatory pathways. Indeed, recent genetic association studies show that polymorphisms in candidate genes related to inflammatory signaling, vascular ossification, and oxidative stress response influence the uremic phenotype. DNA polymorphisms may also be used as nonconfounded tools in observational studies conducted to test causality, as stated by the mendelian randomization approach. To date, the collection of genetic data is no longer a limitation because genetic information is easily accessible in public databases and high-throughput genotyping technologies are available. Advanced bioinformatic tools are now warranted to facilitate the integration of accumulating genetic information with clinical and biochemical end points and, finally, to implement genotype-phenotype data in the care of patients with renal failure to better identify patients at high risk and to design novel personalized therapeutic and preventive strategies.
authors.affiliation: Department of Molecular Medicine and Surgery, Neurogenetics Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Witasp
authors.forename: Louise
authors.initials: L
authors.lastname: Nordfors
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
mesh_terms: D002114:Calcinosis / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000401:mortality; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000401:mortality; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014511:Uremia / Q000235:genetics*