Association entre les variantes génétiques de l’interleukine-1β et une prolongation de l’intervalle QTc après une chirurgie cardiaque: une étude observationnelle prospective

Translated title of the contribution: Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study

M. Kertai, Yunqi Ji, Yi Ju Li, Joseph P. Mathew, James P. Daubert, Mihai V. Podgoreanu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. Methods: All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes –involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes– was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. Results: After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). Conclusion: The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.

Original languageFrench
Pages (from-to)397-410
Number of pages14
JournalCanadian Journal of Anaesthesia
Volume63
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

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Interleukin-1
Thoracic Surgery
Observational Studies
Single Nucleotide Polymorphism
Prospective Studies
Odds Ratio
Confidence Intervals
Genes
Genetic Models
Cardiac Arrhythmias
Electrocardiography
Cytokines

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Association entre les variantes génétiques de l’interleukine-1β et une prolongation de l’intervalle QTc après une chirurgie cardiaque : une étude observationnelle prospective. / Kertai, M.; Ji, Yunqi; Li, Yi Ju; Mathew, Joseph P.; Daubert, James P.; Podgoreanu, Mihai V.

In: Canadian Journal of Anaesthesia, Vol. 63, No. 4, 01.04.2016, p. 397-410.

Research output: Contribution to journalArticle

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title = "Association entre les variantes g{\'e}n{\'e}tiques de l’interleukine-1β et une prolongation de l’intervalle QTc apr{\`e}s une chirurgie cardiaque: une {\'e}tude observationnelle prospective",
abstract = "Background: We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. Methods: All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes –involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes– was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. Results: After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95{\%} confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95{\%} CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). Conclusion: The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.",
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AU - Ji, Yunqi

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AU - Podgoreanu, Mihai V.

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