Abstract 950 Gremlin-1 and macrophage migration inhibitory factor polymorphisms are associated with adverse clinical outcome in patients with symptomatic artery disease

Clin Res Cardiol (2021) DOI DOI https://doi.org/10.1007/s00392-021-01843-w
Gremlin-1 and macrophage migration inhibitory factor polymorphisms are associated with adverse clinical outcome in patients with symptomatic artery disease
K. A. L. Müller¹, K.-P. Kreisselmeier¹, L. P. Hack¹, E. Schaeffeler², M. Gawaz¹, S. Winter², M. Schwab², I. I. Müller¹, T. Geisler¹, D. Rath¹
¹Innere Medizin III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Tübingen; ²Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart;
Objectives: Macrophage Migration Inhibitory Factor (MIF) and its endogenous antagonist Gremlin-1 play a pivotal role in pro-inflammatory and pro-fibrotic processes in atherogenesis and atheroprogression in coronary artery disease (CAD). Therefore, we hypothesized that clinically relevant single nucleotide polymorphisms (SNPs) of MIF and Gremlin-1 are associated with clinical outcome of patients with symptomatic CAD. Methods and Results: Genotyping for selected Gremlin-1 (rs1129456, rs4779584) and MIF (rs2070767, rs755622) variants was performed in n=943 consecutive patients with symptomatic CAD who underwent percutaneous coronary intervention (PCI). All patients were followed after PCI for the occurrence of adverse clinical events including all-cause death (ACD), myocardial infarction (MI), ischemic stroke (IS), and bleeding for a mean follow-up of 1080 days after study inclusion. The combined primary endpoint (CE) consisted of either ACD, MI and/or IS. Secondary endpoints included the single events of ACD, MI, IS, and bleeding. We compared minor allele carriers (both heterozygous and homozygous) of both Gremlin-1 rs1129456 and Gremlin-1 rs4779584 with homozygous carriers of the major allele of both Gremlin-1 rs1129456 and Gremlin-1 rs4779584. We also performed these analyses for the MIF variants rs2070767 and rs755622. There were no differences in the occurrence of CE. By using a recessive genetic model, we found associations of the Gremlin-1 rs1129456 variant (p= 0.012) with the occurrence of IS during follow-up as well as for the MIF rs2070767 variant (p= 0.014). However, after adjusting for multiple testing, these associations did not remain statistically significant. We could not find significant differences for CE, ACD, MI and bleeding. Conclusion: Gremlin-1 rs1129456 and rs4779584 as well as MIF rs2070767 and rs755622 are not associated with prognosis in patients with symptomatic cardiovascular disease. These SNPs might not serve as targets for risk stratification and tailoring therapies in patients with cardiovascular disease.
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