Principal Investigator (PI)
Barbara Kollerits , Claudia Lamina , Hans Dieplinger
There exists accumulating evidence from in vitro studies that apolipoprotein A-IV (apoA-IV) plays an important role in reverse cholesterol transport. Our group focuses on the following research issues related to apoA-IV.
ApoA-IV in patients with atherosclerotic complications
We demonstrated for the first time that decreased plasma concentrations of apoA-IV are associated with atherosclerotic complications. This association was observed in the general population (Figure 1) as well as in patients with chronic kidney disease.
ApoA-IV in patients with renal disease
In patients with renal disease we observed that apoA-IV concentrations start to increase during the earliest phases of renal impairment making apoA IV to an early marker of renal impairment (Figure 2).
Dialysis patients have twice as high plasma concentrations than healthy controls. In the “Mild to Moderate Kidney Disease Study” (MMKD) we found that the presence of high concentrations of apoA-IV is a reliable predictor for a progression of kidney disease during the following years of observation. This association was independent from the baseline glomerular filtration rate and proteinuria (Figure 3).
Genetic regulation of apoA-IV concentrations
We published the first genome-wide association study in 2016. We identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1. The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles (Figure 4). Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations.
GCKD study, KORA Study Group, SAPHIR Study, Bruneck Study, Utah Obesity Case-Control Study, CoLaus Study, Cardiovascular Risk in Young Finns Study, Rotterdam Study, CAVASIC Study
Earlier Team Members
Schwaiger Johannes, Salome Mack, Stephanie Stangl, Marina Haiman, Benjamin Ezeh, Evi Trenkwalder, Eva Boes, Arno Lingenhel, Doreen Dähnhardt
Schwaiger JP, Kollerits B, Steinbrenner I, Weissensteiner H, Schönherr S, Forer L, Kotsis F, Lamina C, Schneider MP, Schultheiss UT, Wanner C, Köttgen A, Eckardt KU, Kronenberg F, GCKD Investigators: Apolipoprotein A-IV concentrations and clinical outcomes in a large chronic kidney disease cohort: Results from the GCKD study. J. Intern. Med. 291:622-636, 2022. PMID: 34914850
Lamina C, Friedel S, Coassin S, Rueedi R, Yousri NA, Seppälä I, Gieger C, Schönherr S, Forer L, Erhart G, Kollerits B, Marques-Vidal P, Ried J, Waeber G, Bergmann S, Dähnhardt D, Stöckl A, Kiechl S, Raitakari OT, Kähönen M, Willeit J, Kedenko L, Paulweber B, Peters A, Meitinger T, Strauch K, KORA Study Group, Lehtimäki T, Hunt SC, Vollenweider P, Kronenberg F: A genome-wide association meta-analysis on apolipoprotein A-IV concentrations. Hum. Mol. Genet. 25:3635-3646, 2016. PMID: 27412012
Mack S, Coassin S, Vaucher J, Kronenberg F, Lamina C, ApoA-IV-GWAS Consortium: Evaluating the causal relation of ApoA-IV with disease-related traits - A bidirectional two-sample Mendelian randomization study. Sci. Rep. 7:8734, 2017. PMID: 28821713
Kronenberg F: Apolipoprotein L1 and apolipoprotein A-IV and their association with kidney function. Curr. Opin. Lipidol. 28:39-45, 2017. PMID: 27870653
Stangl S, Kollerits B, Lamina C, Meisinger C, Huth C, Stöckl A, Dähnhardt D, Böger CA, Krämer BK, Peters A, Kronenberg F: Association between apolipoprotein A-IV concentrations and chronic kidney disease in two large population-based cohorts: results from the KORA studies. J. Intern. Med. 278:410-423, 2015. PMID: 26037138
Kollerits B, Krane V, Drechsler C, Lamina C, März W, Ritz E, Wanner C, Kronenberg F, German Diabetes and Dialysis Study Investigators: Apolipoprotein A-IV concentrations and clinical outcomes in haemodialysis patients with type 2 diabetes mellitus–a post hoc analysis of the 4D Study. J. Intern. Med. 272:592-600, 2012. PMID: 22891946
Kronenberg F: Emerging risk factors and markers of chronic kidney disease progression. Nat. Rev. Nephrol. 5:677-689, 2009. PMID: 19935815
Lingenhel A, Lhotta K, Neyer U, Heid IM, Rantner B, Kronenberg MF, König P, von Eckardstein A, Schober M, Dieplinger H, Kronenberg F: Role of the kidney in the metabolism of apolipoprotein A-IV: influence of the type of proteinuria. J. Lipid Res. 47:2071-2079, 2006. PMID: 16788210
Boes E, Fliser D, Ritz E, König P, Lhotta K, Mann JF, Müller GA, Neyer U, Riegel W, Riegler P, Kronenberg F: Apolipoprotein A-IV predicts progression of chronic kidney disease: the mild to moderate kidney disease study. J. Am. Soc. Nephrol. 17:528-536, 2006. PMID: 16382017
Haiman M, Salvenmoser W, Scheiber K, Lingenhel A, Rudolph C, Schmitz G, Kronenberg F, Dieplinger H: Immunohistochemical localization of apolipoprotein A-IV in human kidney tissue. Kidney Int. 68:1130-1136, 2005. PMID: 16105043