title: Association of functional kallikrein-1 promoter polymorphisms and acute kidney injury: a case-control and longitudinal cohort study.
abstract: BACKGROUND
  Kallikrein-1 (KLK1) is a highly conserved serine protease that is expressed in the kidney and involved in blood pressure regulation. The activity of this enzyme is diminished in acute kidney injury (AKI).
  
  
  METHODS
  We first evaluated the potential role of functional multiallelic KLK1 promoter gene polymorphisms in a case-control study of 481 subjects (214 hospitalized patients with AKI of mixed causes and 267 healthy subjects). The complex, multiallelic G/C-rich repeat region of the proximal KLK1 promoter was determined by direct Sanger/capillary resequencing.
  
  
  RESULTS
  16 alleles were identified in a complex, polymorphic G/C-rich region of the KLK1 proximal promoter; 5 of these alleles (F, G, H, I, and K) were associated with development of AKI. Alleles I and G were classified as risk-alleles (unadjusted OR 1.86; 95% CI 1.23, 2.81; p = 0.003), whereas alleles F, H, and K were classified as protective-alleles (unadjusted OR 0.32; 95% CI 0.22, 0.46; p < 0.001) according to their directional association with development of AKI. After adjustment for sex, race, preexisting chronic kidney disease and APACHE II score, the KLK1 risk-allele (I or G) carrier state was associated with the composite of ≥2-fold increase in serum creatinine, oliguria, or dialysis requirement (adjusted OR 2.71; 95% CI 1.14, 6.44; p = 0.02). The KLK1 risk-allele carrier state was also marginally associated with the composite of ≥2-fold increase in serum creatinine, oliguria, dialysis requirement, or in-hospital death (adjusted OR 2.33; 95% CI 0.98, 5.52; p = 0.06).
  
  
  CONCLUSIONS
  KLK1 promoter polymorphisms are associated with development of AKI and adverse outcomes. Further studies are needed to validate these findings.
authors: Department of Medicine, Division of Nephrology, Kidney and Dialysis Research Laboratory, St. Elizabeth's Medical Center, Boston, Mass., USA.
authors: Paweena
authors: P
authors: Susantitaphong
authors: Mary C
authors: MC
authors: Perianayagam
authors: Sun Woo
authors: SW
authors: Kang
authors: Wenyi
authors: W
authors: Zhang
authors: Fangwen
authors: F
authors: Rao
authors: Daniel T
authors: DT
authors: O'Connor
authors: Bertrand L
authors: BL
authors: Jaber
mesh_terms: D058186:Acute Kidney Injury / Q000453:epidemiology* / Q000235:genetics*; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001900:Boston / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018570:Risk Assessment; D017678:Sex Distribution; D020840:Tissue Kallikreins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D020840:Tissue Kallikreins
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