BCL2 genetic variants are associated with acute kidney injury in septic shock

Angela J. Frank, Chau Chyun Sheu, Yang Zhao, Feng Chen, Li Su, Michelle Ng Gong, Ednan Bajwa, B. Taylor Thompson, David C. Christiani

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: Acute kidney injury frequently complicates septic shock and independently predicts mortality in this population. Clinical factors alone do not entirely account for differences in risk of acute kidney injury between patients. Genetic variants are likely to explain this differential susceptibility. To identify genetic variants linked to acute kidney injury susceptibility, we conducted a high-density genotyping association study in a large population of patients with septic shock. Design: Retrospective study. Setting: Tertiary academic medical center. Patients: One thousand two hundred and sixty-four patients with septic shock were analyzed to elucidate clinical risk factors associated with the development of acute kidney injury. Among them, 887 Caucasian patients were randomly split into discovery and validation cohorts and genotyped using the Illumina Human-CVD BeadChip (Illumina, San Diego, CA). Interventions: None. Measurements and Main Results: Six hundred and twenty-seven of the 1,264 patients with septic shock and 441 of the 887 patients with genotyping data developed acute kidney injury within the first 72 hrs of intensive care unit admission. Five single nucleotide polymorphisms were associated with acute kidney injury in both the discovery and validation cohorts. Two of these were in the BCL2 gene and both were associated with a decreased risk of acute kidney injury (rs8094315: odds ratio 0.61, p = .0002; rs12457893: odds ratio 0.67, p = .0002, both for combined data). Bcl-2 is involved in the apoptosis pathway, which has previously been implicated in acute kidney injury. Another single nucleotide polymorphism was in the SERPINA4 gene, whose protein product, kallistatin, has been linked to apoptosis in the kidney. Conclusions: Large-scale genotyping reveals two single nucleotide polymorphisms in the BCL2 gene and a single nucleotide polymorphism in the SERPINA4 gene associated with a decreased risk of developing acute kidney injury, supporting the putative role of apoptosis in the pathogenesis of acute kidney injury.

Original languageEnglish (US)
Pages (from-to)2116-2123
Number of pages8
JournalCritical Care Medicine
Volume40
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Septic Shock
Acute Kidney Injury
Single Nucleotide Polymorphism
Apoptosis
Odds Ratio
Genes
Population
Intensive Care Units
Retrospective Studies
Kidney
Mortality

Keywords

  • Acute kidney injury
  • apoptosis
  • BCL2
  • genetic susceptibility
  • sepsis
  • SERPINA4

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Frank, A. J., Sheu, C. C., Zhao, Y., Chen, F., Su, L., Gong, M. N., ... Christiani, D. C. (2012). BCL2 genetic variants are associated with acute kidney injury in septic shock. Critical Care Medicine, 40(7), 2116-2123. https://doi.org/10.1097/CCM.0b013e3182514bca

BCL2 genetic variants are associated with acute kidney injury in septic shock. / Frank, Angela J.; Sheu, Chau Chyun; Zhao, Yang; Chen, Feng; Su, Li; Gong, Michelle Ng; Bajwa, Ednan; Taylor Thompson, B.; Christiani, David C.

In: Critical Care Medicine, Vol. 40, No. 7, 07.2012, p. 2116-2123.

Research output: Contribution to journalArticle

Frank, AJ, Sheu, CC, Zhao, Y, Chen, F, Su, L, Gong, MN, Bajwa, E, Taylor Thompson, B & Christiani, DC 2012, 'BCL2 genetic variants are associated with acute kidney injury in septic shock', Critical Care Medicine, vol. 40, no. 7, pp. 2116-2123. https://doi.org/10.1097/CCM.0b013e3182514bca
Frank, Angela J. ; Sheu, Chau Chyun ; Zhao, Yang ; Chen, Feng ; Su, Li ; Gong, Michelle Ng ; Bajwa, Ednan ; Taylor Thompson, B. ; Christiani, David C. / BCL2 genetic variants are associated with acute kidney injury in septic shock. In: Critical Care Medicine. 2012 ; Vol. 40, No. 7. pp. 2116-2123.
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AU - Zhao, Yang

AU - Chen, Feng

AU - Su, Li

AU - Gong, Michelle Ng

AU - Bajwa, Ednan

AU - Taylor Thompson, B.

AU - Christiani, David C.

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AB - Objective: Acute kidney injury frequently complicates septic shock and independently predicts mortality in this population. Clinical factors alone do not entirely account for differences in risk of acute kidney injury between patients. Genetic variants are likely to explain this differential susceptibility. To identify genetic variants linked to acute kidney injury susceptibility, we conducted a high-density genotyping association study in a large population of patients with septic shock. Design: Retrospective study. Setting: Tertiary academic medical center. Patients: One thousand two hundred and sixty-four patients with septic shock were analyzed to elucidate clinical risk factors associated with the development of acute kidney injury. Among them, 887 Caucasian patients were randomly split into discovery and validation cohorts and genotyped using the Illumina Human-CVD BeadChip (Illumina, San Diego, CA). Interventions: None. Measurements and Main Results: Six hundred and twenty-seven of the 1,264 patients with septic shock and 441 of the 887 patients with genotyping data developed acute kidney injury within the first 72 hrs of intensive care unit admission. Five single nucleotide polymorphisms were associated with acute kidney injury in both the discovery and validation cohorts. Two of these were in the BCL2 gene and both were associated with a decreased risk of acute kidney injury (rs8094315: odds ratio 0.61, p = .0002; rs12457893: odds ratio 0.67, p = .0002, both for combined data). Bcl-2 is involved in the apoptosis pathway, which has previously been implicated in acute kidney injury. Another single nucleotide polymorphism was in the SERPINA4 gene, whose protein product, kallistatin, has been linked to apoptosis in the kidney. Conclusions: Large-scale genotyping reveals two single nucleotide polymorphisms in the BCL2 gene and a single nucleotide polymorphism in the SERPINA4 gene associated with a decreased risk of developing acute kidney injury, supporting the putative role of apoptosis in the pathogenesis of acute kidney injury.

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KW - sepsis

KW - SERPINA4

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