Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery – a sub-analysis of the RIPHeart-Study

Abstract

BackgroundThe aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery.MethodsWe conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery.ResultsA total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10− 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10− 5 from the GWAS.ConclusionsWe identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery.Trial registrationThe study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.Electronic supplementary materialThe online version of this article (10.1186/s12872-019-1002-x) contains supplementary material, which is available to authorized users.

Potential Value of TNF-α (–376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients

“…Similar to other reports, a significant association has been shown between the minor allele (A) of TNF-α (-308 G/ A) and the severity of AKI (Susantitaphong et al, 2013), and organ dysfunctions in septic patients (Wang et al, 2017). In contrast, a larger study did not find any association between the above SNPs with AKI (Westphal et al, 2019). Likewise, TNF-α (-308) polymorphism was not associated with progression into AKI in patients with severe sepsis (Payen, 2019), and in patients following cardiac surgical interventions (Boehm et al, 2014).…”

DUSP4 alleviates LPS‑induced chondrocyte injury in knee osteoarthritis via the MAPK signaling pathway

“…Human chondrocytes will be used for verification in future experiments. Emerging evidence has demonstrated that DUSP4 serves a regulatory role in cell inflammation, injury and apoptosis in a variety of diseases (9,22,23). However, the exact mechanism underlying DUSP4 in OA is yet to be elucidated.…”

The Macrophage Migration Inhibitory Factor (MIF) Promoter Polymorphisms (rs3063368, rs755622) Predict Acute Kidney Injury and Death after Cardiac Surgery

“…In the same study cohort, one genome-wide association study (GWAS) has been undertaken and did not identify an association of the MIF gene polymorphisms with postoperative outcome [ 47 ]. Therefore, our findings underscore the necessity of candidate gene studies, including of common structural variants such as microsatellite repeats that are not detectable by SNP-based GWAS platforms [ 47 , 48 , 49 ].…”

“…In the same study cohort, one genome-wide association study (GWAS) has been undertaken and did not identify an association of the MIF gene polymorphisms with postoperative outcome [ 47 ]. Therefore, our findings underscore the necessity of candidate gene studies, including of common structural variants such as microsatellite repeats that are not detectable by SNP-based GWAS platforms [ 47 , 48 , 49 ]. As technological advances and declining costs in next-generation sequencing technologies pave the way for the broader availability of genomic testing, the implementation of genetic susceptibility data will help to improve risk stratification and to reduce the incidence and sequelae of cardiac surgery [ 50 ].…”