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BCL2 genetic variants are associated with acute kidney injury in septic shock
Critical Care Medicine, 06/22/2012
Frank AJ et al. – 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.
Methods- 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)
- 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 72hrs 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.