CYBA Gene Polymorphisms and Adverse Outcomes in Acute Kidney Injury: A Prospective Cohort Study

Background: NADPH oxidase is an important enzyme involved in the generation of reactive oxygen species in acute kidney injury (AKI). Its key subunit, p22(phox), is encoded by the highly polymorphic CYBA gene.

Methods: We examined the associations of CYBA gene polymorphisms across the CYBA locus (rs8854, rs3794624, rs4673, rs4782390, and rs1049255) with dialysis requirement or in-hospital death in 256 hospitalized adults with AKI. Dominant and haplotype multivariable logistic regression analyses were performed, adjusted for sex, race, age, and severity of illness.

Results: The baseline characteristics of the patients were not different among genotype groups with the exception of a lower prevalence of sepsis and shock in the CYBA rs8854 A-allele group; a higher prevalence of shock in the CYBA rs4782390 T-allele group, and a higher APACHE II score in the CYBA rs1049255 G-allele group. The CYBA rs8854 A-allele had an adjusted odds ratio (OR) of 0.41 (95% confidence interval, CI, 0.18-0.96) for the outcome of dialysis requirement or in-hospital death. The CYBA rs4673 T-allele and rs1049255 G-allele had unadjusted ORs of 1.69 (95% CI 1.03-2.79) and 1.66 (95% CI 1.01-2.73) for the composite outcome, respectively, which became non-significant after multivariable adjustment. The remaining 2 polymorphisms were not associated with the outcomes of interest. Finally, the presence of the CYBA A-A-G-G haplotype (generated from rs4782390, rs4673, rs3794624, and rs8854, all in Hardy-Weinberg equilibrium) was associated with an elevated OR of 1.81 (95% CI 1.07-3.08) for dialysis requirement or in-hospital death, which was attenuated after multivariable adjustment (OR 1.80; 95% CI 0.99-3.29).

Conclusion: This study identifies several polymorphisms spanning the entire CYBA gene locus and a common haplotype as risk markers for dialysis requirement or in-hospital death in patients with AKI. Additional studies are needed to validate these findings.