Genetic control of postoperative systemic inflammatory reaction and pulmonary and renal complications after coronary artery surgery

Gaudino, Mario; Castelnuovo, Augusto Di; Zamparelli, Roberto; Andreotti, Felicita; Burzotta, Francesco; Iacoviello, Licia; Glieca, Franco; Alessandrini, Francesco; Nasso, Giuseppe; Donati, Maria Benedetta; Maseri, Attilio; Schiavello, R; Possati, Gianfederico

doi:10.1016/s0022-5223(03)00396-9

Cited by 72 publications

(44 citation statements)

References 16 publications

(26 reference statements)

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“…28 On the contrary, studies by Bittar et al 29 show that patients homozygous for the G allele had a significantly lower incidence of postoperative atrial fibrillation and a shorter hospital stay. These differences might occur due to the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction.…”

Section: Discussionmentioning

confidence: 97%

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

et al. 2010

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Background: The interleukin-6 (IL-6) promoter 2174G/C polymorphism (rs1800795) is associated with enhanced systemic inflammatory response to injury. However, data on the effect of this polymorphism on inflammatory markers in patients undergoing coronary artery bypass grafting surgery (CABG) are inconsistent. The aim of our study was to investigate whether 2174G/C IL-6 polymorphism affects plasma IL-6 and C-reactive protein (CRP) concentrations in patients undergoing CABG. Methods: A total of 179 consecutive white patients (77% men, aged 65 + 8.6 standard deviation [SD] y) scheduled for elective isolated CABG were studied. Pre-and postoperative CRP and IL-6 levels were analysed in relation to the 174G/C IL-6 polymorphism determined by using TaqMan single-nucleotide polymorphism genotyping technique. Results: The genotype distribution was as follows: GG -46 (26%), GC -93 (52%) and CC -40 (22%). The C allele carriers had higher baseline CRP (4.1 + 0.35 versus 2.4 + 0.59 mg/L, P ¼ 0.02) and IL-6 levels (3.0 + 0.17 versus 2.2 + 0.3 pg/mL, P ¼ 0.02) than GG patients. Five to seven days after CABG, CRP levels rose by 54% (P ¼ 0.03), and IL-6 levels tended to be higher (P ¼ 0.07) in 2174C allele carriers than the non-carriers. There were no associations between 2174G/C IL-6 polymorphism and any demographic-, clinical-or procedure-related variables as well as major adverse cardiovascular events. Multivariate regression analysis, including sex, age, body mass index, hypercholesterolaemia, smoking, hypertension diabetes, identified CG þ CC genotype as the only independent predictor of preoperative CRP and IL-6 levels. Conclusions: The presence of the 2174C allele determines to some extent higher plasma CRP and IL-6 concentrations pre-and postoperatively in CABG patients.

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Section: Discussionmentioning

confidence: 97%

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

et al. 2010

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“…The IL-6 Ϫ174G/C polymorphism was investigated in three studies, of which only Guadino et al (14) found a significant association. This study found that in patients undergoing CABG, IL-6 Ϫ174GG, carriers had significantly higher elevations in perioperative creatinine versus non-GG carriers (P Ͻ 0.0001).…”

Section: ) Treszl Et Al Also Investigated This Polymorphism In Vlmentioning

confidence: 99%

“…This has been seen in other complex diseases, such as the discovery of a single nucleotide polymorphism (SNP) in complement factor H as a risk factor for macular degeneration (13). In AKI, genetic variation in inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-␣) and Interleukin-6 (IL-6) have recently been proposed as risk factors (11,(14)(15)(16)(17). This is due to the role of inflammatory mediators in the pathophysiology of AKI, especially with ischemia and sepsis (1,18,19).…”

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confidence: 99%

Searching for Genes That Matter in Acute Kidney Injury

Coca

Patel

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and Objectives: Identifying patients who may develop acute kidney injury (AKI) remains challenging, asclinical determinants explain only a portion of individual risk. Another factor that likely affects risk is intrinsic genetic variability. Therefore, a systematic review of studies was performed that related the development or prognosis of AKI to genetic variation.Design, setting, participants, and measurements: MEDLINE, EMBASE, HuGEnet, SCOPUS, and Web of Science were searched for articles from 1950 to Dec 2007. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality via an aggregate scoring system. Results: The 16 included studies were of cohort or case-cohort design and investigated 35 polymorphisms in 21 genes in association with AKI. Fifteen gene-gene interactions were also investigated in four separate studies. Study populations were primarily premature infants or adults who were critically ill or postcardiac bypass patients. Among the studies, five different definitions of AKI were used. Only one polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (P < 0.05) on AKI incidence. The mean quality score of 5.8/10 (range four to nine), heterogeneity in the studies, and the dearth of studies precluded additional meta-analysis of the results.Conclusions: Current association studies are unable to provide definitive evidence linking genetic variation to AKI. Future success will require a narrow consensus definition of AKI, rigorous epidemiologic techniques, and a shift from a priori hypothesis-driven to genome-wide association studies.

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“…Former research suggests that genetic diversity contributes to CSA-AKI. [5][6][7][8][9][10][11][12][13] Perioperative genetics have become an emerging field in recent years as clinicians could be enabled to strengthen existing clinical scores by also considering genetic risk factors predisposing to CSA-AKI.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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.

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Genetic control of postoperative systemic inflammatory reaction and pulmonary and renal complications after coronary artery surgery

Abstract: The interleukin 6 -174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.

Cited by 72 publications

References 16 publications

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6−174G > C gene polymorphism

Searching for Genes That Matter in Acute Kidney Injury

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

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