title: Genotypic and phenotypic predictors of inflammation in patients with chronic kidney disease.
abstract: In complex diseases such as chronic kidney disease (CKD), the risk of clinical complications is determined by interactions between phenotypic and genotypic factors. However, clinical epidemiological studies rarely attempt to analyse the combined effect of large numbers of phenotype and genotype features. We have recently shown that the relaxed linear separability (RLS) model of feature selection can address such complex issues. Here, it is applied to identify risk factors for inflammation in CKD.
  
  
  
  The RLS model was applied in 225 CKD stage 5 patients sampled in conjunction with dialysis initiation. Fifty-seven anthropometric or biochemical measurements and 79 genetic polymorphisms were entered into the model. The model was asked to identify phenotypes and genotypes that, when combined, could separate inflamed from non-inflamed patients. Inflammation was defined as a high-sensitivity C-reactive protein concentration above the median (5 mg/L).
  
  
  
  Among the 60 genotypic and phenotypic features predicting inflammation, 31 were genetic. Among the 10 strongest predictors of inflammation, 8 were single nucleotide polymorphisms located in the NAMPT, CIITA, BMP2 and PIK3CB genes, whereas fibrinogen and bone mineral density were the only phenotypic biomarkers.
  
  
  
  These results indicate a larger involvement of hereditary factors in inflammation than might have been expected and suggest that inclusion of genotype features in risk assessment studies is critical. The RLS model demonstrates that inflammation in CKD is determined by an extensive panel of factors and may prove to be a suitable tool that could enable a much-needed multifactorial approach as opposed to the commonly utilized single-factor analysis.
authors.affiliation: Department of Molecular Medicine and Surgery, Neurogenetics Division, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Luttropp
authors.affiliation: Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Debowska
authors.affiliation: Bialystok University of Technology, Bialystok, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lukaszuk
authors.affiliation: Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.|Bialystok University of Technology, Bialystok, Poland.
authors.forename: Leon
authors.initials: L
authors.lastname: Bobrowski
authors.affiliation: Department of Molecular Medicine and Surgery, Neurogenetics Division, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Juan Jesus
authors.initials: JJ
authors.lastname: Carrero
authors.affiliation: Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.affiliation: Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.affiliation: Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.affiliation: Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Waniewski
authors.affiliation: Department of Molecular Medicine and Surgery, Neurogenetics Division, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Nordfors
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D015519:Bone Density; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: biomarkers; dialysis; end-stage renal disease; gene polymorphism; inflammation; relaxed linear separability