OBJECTIVES: The LPA I4399M (rs3798220) single nucleotide polymorphism (SNP) is associated with increased plasma levels of Lp(a) and advanced coronary artery disease (CAD). We hypothesized that carriers of the Met allele of the I4399M SNP would also have elevated levels of oxidized phospholipids (OxPL) on apoB (OxPL/apoB) particles. METHODS AND RESULTS: Plasma levels of Lp(a) and OxPL/apoB were measured in non-carriers (TT genotype, n=116) and carriers (CT/CC genotype, n=58) of the I4399M SNP. Carriers had significantly higher Lp(a) levels [median (interquartile range, IQR)] [43 (9-57)mg/dl vs. 5.5 (2-20)mg/dl, p<0.0001] and smaller apolipoprotein(a) isoforms than non-carriers (number of kringle IV repeats: 18(17-20) vs. 22(18-25), p=0.002). Median (IQR) OxPL/apoB levels were significantly higher in carriers than non-carriers [8019 (6254-31,785) relative light units (RLU) vs. 2168 (1303-5869), p<0.0001]. Patients with small apolipoprotein(a) isoforms had the highest OxPL/apoB levels. The number of kringle IV repeats was inversely related to Lp(a) (r=-0.43, p<0.001) and OxPL/apoB (r=-0.36, p<0.0001) levels. CONCLUSION: The CT and CC genotypes of the I4399M SNP in the LPA gene are associated with elevated OxPL/apoB levels, which primarily represent OxPL on Lp(a). The concomitant increase of OxPL/apoB levels in the setting of small apolipoprotein(a) isoforms may potentiate the atherogenic effect on CAD of elevated Lp(a) levels in carriers of the I4399M SNP. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
OBJECTIVES: The LPA I4399M (rs3798220) single nucleotide polymorphism (SNP) is associated with increased plasma levels of Lp(a) and advanced coronary artery disease (CAD). We hypothesized that carriers of the Met allele of the I4399M SNP would also have elevated levels of oxidized phospholipids (OxPL) on apoB (OxPL/apoB) particles. METHODS AND RESULTS: Plasma levels of Lp(a) and OxPL/apoB were measured in non-carriers (TT genotype, n=116) and carriers (CT/CC genotype, n=58) of the I4399M SNP. Carriers had significantly higher Lp(a) levels [median (interquartile range, IQR)] [43 (9-57)mg/dl vs. 5.5 (2-20)mg/dl, p<0.0001] and smaller apolipoprotein(a) isoforms than non-carriers (number of kringle IV repeats: 18(17-20) vs. 22(18-25), p=0.002). Median (IQR) OxPL/apoB levels were significantly higher in carriers than non-carriers [8019 (6254-31,785) relative light units (RLU) vs. 2168 (1303-5869), p<0.0001]. Patients with small apolipoprotein(a) isoforms had the highest OxPL/apoB levels. The number of kringle IV repeats was inversely related to Lp(a) (r=-0.43, p<0.001) and OxPL/apoB (r=-0.36, p<0.0001) levels. CONCLUSION: The CT and CC genotypes of the I4399M SNP in the LPA gene are associated with elevated OxPL/apoB levels, which primarily represent OxPL on Lp(a). The concomitant increase of OxPL/apoB levels in the setting of small apolipoprotein(a) isoforms may potentiate the atherogenic effect on CAD of elevated Lp(a) levels in carriers of the I4399M SNP. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Authors: Gregor Leibundgut; Corey Scipione; Huiyong Yin; Matthias Schneider; Michael B Boffa; Simone Green; Xiaohong Yang; Edward Dennis; Joseph L Witztum; Marlys L Koschinsky; Sotirios Tsimikas Journal: J Lipid Res Date: 2013-07-04 Impact factor: 5.922
Authors: Fangwen Rao; Andrew J Schork; Adam X Maihofer; Caroline M Nievergelt; Santica M Marcovina; Elizabeth R Miller; Joseph L Witztum; Daniel T O'Connor; Sotirios Tsimikas Journal: Arterioscler Thromb Vasc Biol Date: 2015-05-07 Impact factor: 8.311
Authors: Salome Mack; Stefan Coassin; Rico Rueedi; Noha A Yousri; Ilkka Seppälä; Christian Gieger; Sebastian Schönherr; Lukas Forer; Gertraud Erhart; Pedro Marques-Vidal; Janina S Ried; Gerard Waeber; Sven Bergmann; Doreen Dähnhardt; Andrea Stöckl; Olli T Raitakari; Mika Kähönen; Annette Peters; Thomas Meitinger; Konstantin Strauch; Ludmilla Kedenko; Bernhard Paulweber; Terho Lehtimäki; Steven C Hunt; Peter Vollenweider; Claudia Lamina; Florian Kronenberg Journal: J Lipid Res Date: 2017-05-16 Impact factor: 5.922