Hypoxia-Inducible Factor-1α Stabilizing Genetic Variant and Adverse Outcomes in Acute Kidney Injury
| Autor: | Kolyada, Alexey Y., Tighiouart, Hocine, Perianayagam, Mary C., Liangos, Orfeas, Madias, Nicolaos E., Jaber, Bertrand L. |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Aged
80 and over Male Vascular Endothelial Growth Factor A Base Sequence Genotype Angiotensin II Genetic Variation Acute Kidney Injury Middle Aged Hypoxia-Inducible Factor 1 alpha Subunit Prognosis Polymorphism Single Nucleotide Respiration Artificial Article Cohort Studies Renal Dialysis Humans Female Prospective Studies Alleles Aged DNA Primers |
| Popis: | Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that mediates many cellular responses to tissue hypoxia, a common feature of acute kidney injury (AKI). Here we studied 241 patients with AKI and determined the relationship to adverse outcome of a non-synonymous polymorphism in the coding region of the HIF-1alpha gene where a C to T substitution occurs at position +85 in exon 12, a change known to enhance transactivation. The baseline characteristics of the patients were not different among genotype groups except for a significantly higher prevalence of shock and number of failed organs in T-allele carriers. A significant genotype-phenotype association was found for plasma levels of vascular endothelial growth factor-A but not angiopoietin-2, two downstream targets of HIF-1alpha. Compared to the CC genotype, T-allele carriers had significantly higher adjusted odds for dialysis requirement or in-hospital death; assisted mechanical ventilation or dialysis requirement; and the composite of assisted mechanical ventilation, dialysis requirement or in-hospital death. The trend for higher plasma angiopoietin-2 levels was associated with significantly higher adjusted odds for in-hospital death; dialysis requirement or in-hospital death; and the composite outcome of assisted mechanical ventilation, dialysis, or in-hospital death. Despite the limited cohort size, our study found this particular HIF-1alpha genetic variant to be associated with disease severity and adverse outcomes in AKI. Larger studies are needed to confirm these relationships. |
| Databáze: | OpenAIRE |
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