title: Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery.
abstract: Genetic variants within the endothelin-1 gene (EDN1) have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint). The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy-Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T) haplotype had a higher cardiac index than did non-carriers (p = 0.0008); however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery.
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: Ashham
authors.initials: A
authors.lastname: Mansur
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Steinau
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Support, Royal Brompton and Harefield Hospital, Harefield, Hill End Road, UB9 6JH London, United Kingdom.
authors.forename: Aron Frederik
authors.initials: AF
authors.lastname: Popov
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Milenovic
authors.affiliation: Department of Thoracic Cardiovascular Surgery, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bireta
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Support, Royal Brompton and Harefield Hospital, Harefield, Hill End Road, UB9 6JH London, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Weymann
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Schotola
authors.affiliation: Department of Anesthesiology, University of Regensburg, Franz-Josef-Strauß-Allee 11, D-93053 Regensburg, Germany.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Wiese
authors.affiliation: Department of Medical Statistics, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.affiliation: Institute of Clinical Pharmacology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: Mladen
authors.initials: M
authors.lastname: Tzvetkov
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Robert-Koch-Str.40, D-37075 Goettingen, Germany.
authors.forename: José
authors.initials: J
authors.lastname: Hinz
mesh_terms: D006348:Cardiac Surgical Procedures / Q000401:mortality*; D019332:Endothelin-1 / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D017052:Hospital Mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011184:Postoperative Period; D011379:Prognosis
chemical_list: D019332:Endothelin-1