Apolipoprotein E genotype, TNF-α 308G/A and risk for cardiac surgery associated-acute kidney injury in Caucasians

Abstract

Objectives: Acute kidney injury following cardiac surgery depicts a severe clinical problem that is strongly associated with adverse short-and long-term outcome. We analyzed two common genetic polymorphisms that have previously been linked to renal failure and inflammation, and have been supposed to be associated with cardiac surgery associated-acute kidney injury (CSA-AKI). Methods: A total of 1415 consecutive patients who underwent elective cardiac surgery with CPB at our institution were prospectively enrolled. Patients were genotyped for Apolipoprotein E (ApoE E2,E3,E4) (rs429358 and rs7412) and TNF-a-308 G4A (rs1800629). Results: Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between ApoE (E2,E3,E4) and TNF-a-308 G4A genotypes and the RIFLE criteria could be detected. Several multiple linear regression analyses for postoperative creatinine increase revealed highly significant associations for aortic cross clamp time (p50.001), CPB-time (p50.001), norepinephrine (p50.001), left ventricular function (p ¼ 0.004) and blood transfusion (p50.001). No associations were found for ApoE (E2,E3,E4) and TNF-a-308 G4A genotypes or baseline creatinine. When the sample size is 1415, the multiple linear regression test of R 2 ¼ 0 for seven covariates assuming normal distribution will have at least 99% power with significance level 0.05 to detect an R 2 of 0.108 or 0.107 as observed in the data. Conclusions: ApoE (E2,E3,E4) polymorphism and the TNF-a-308 G4A polymorphism are not associated with renal injury after CPB.

Association of genetic polymorphisms with acute kidney injury after cardiac surgery in a Southeast Asian population

“…However, we did not demonstrate any association of ApoE to AKI in our population. This result mirrored the study conducted by Boehm et al, in a German cohort [26].…”

Effects of ECE-1b rs213045 and rs2038089 polymorphisms on the development of contrast-induced acute kidney injury in patients with acute coronary syndrome

“…16 Additionally, Chew et al 15 found that APO-E polymorphism was associated with elevated creatinine after cardiac surgery. In contrast, Boehm et al 21 did not find any significant association between APO-E and TNFa polymorphisms in patients with AKI after cardiac surgery.…”

“…Some studies found that target gene variations were responsible for an increased risk of AKI, [15][16][17][18][19] whereas others found that the variations were not related to the risk of AKI. [20][21][22] ACE I/D and APO-E gene polymorphisms were found to be associated with inflammation and vasoconstriction as well as increased creatinine clearance in a study of genetic polymorphisms affecting AKI development after coronary artery bypass grafting. 16 Additionally, Chew et al 15 found that APO-E polymorphism was associated with elevated creatinine after cardiac surgery.…”

Genetic predisposition to acute kidney injury – a systematic review

“…The non-e4-allele of polymorphisms rs429358 and rs7412 of apolipoprotein E (APOE) have appeared to associate with a higher maximum creatinine [ 24 , 43 ], and with increased risk of postoperative AKI [ 38 ], in two studies unable to find any association in this post-CABG setting [ 36 , 44 ]. A study by Kolyada [ 29 ] showed that the T-allele of an rs11549465 polymorphism +85 C/T on transcription factor hypoxia-inducible factor-1alpha (HIF-1α) gene is associated with higher use of dialysis.…”

“…Polymorphism rs1800629 in the TNFA gene is suspected to alter the inflammatory response and to be associated with AKI susceptibility [ 41 , 45 ], as well as outcome [ 27 , 30 , 41 ]. This finding is controversial, however; in five studies [ 25 , 36 , 40 , 42 , 44 ] no evidence supported an association between TNFA and susceptibility or outcome of AKI. Second, polymorphisms rs429358 and rs7412 in the APOE –gene have been investigated among patients undergoing cardiac surgery.…”