{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rao F"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS"],"pagination":["1704-11"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4483152"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["35(7)"],"pubmed_abstract":["Objective
To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL).Approach and results
We measured oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49; P<0.001) and Lp(a) (R=-0.48; P<0.001) and OxPL-apoB was modestly correlated with Lp(a) (ρ=0.57; P<0.0001). The correlation in major apo(a) isoform size was concordant (R=1.0; P<0.001) among monozygotic twins but not dizygotic twins (R=0.40; P=0.055). Lp(a) and OxPL-apoB shared genetic codetermination (genetic covariance, ρG=0.774±0.032; P=1.09×10(-38)), although not environmental determination (environmental covariance, ρE=0.081±0.15; P=0.15). In contrast, Lp(a) shared environmental but not genetic codetermination with autoantibodies to malondialdehyde-modified low-density lipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a).Conclusions
OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis."],"journal":["Arteriosclerosis, thrombosis, and vascular biology"],"pubmed_title":["Heritability of Biomarkers of Oxidized Lipoproteins: Twin Pair Study."],"pmcid":["PMC4483152"],"funding_grant_id":["P01 HL055798","R01-HL086599","DK094894","P01 HL088093","R01 HL119828","P30 DK079337","R01 DK094894","P01 HL058120","P01-HL055798","R01-HL119828","P01-HL088093","R01-HL093767","HL58120"],"pubmed_authors":["Marcovina SM","Witztum JL","Tsimikas S","Schork AJ","Miller ER","Rao F","O'Connor DT","Maihofer AX","Nievergelt CM"],"additional_accession":[]},"is_claimable":false,"name":"Heritability of Biomarkers of Oxidized Lipoproteins: Twin Pair Study.","description":"Objective
To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL).Approach and results
We measured oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49; P<0.001) and Lp(a) (R=-0.48; P<0.001) and OxPL-apoB was modestly correlated with Lp(a) (ρ=0.57; P<0.0001). The correlation in major apo(a) isoform size was concordant (R=1.0; P<0.001) among monozygotic twins but not dizygotic twins (R=0.40; P=0.055). Lp(a) and OxPL-apoB shared genetic codetermination (genetic covariance, ρG=0.774±0.032; P=1.09×10(-38)), although not environmental determination (environmental covariance, ρE=0.081±0.15; P=0.15). In contrast, Lp(a) shared environmental but not genetic codetermination with autoantibodies to malondialdehyde-modified low-density lipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a).Conclusions
OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jul","modification":"2024-11-12T09:17:45.692Z","creation":"2019-03-27T01:54:08Z"},"accession":"S-EPMC4483152","cross_references":{"pubmed":["25953646"],"doi":["10.1161/ATVBAHA.115.305306","10.1161/atvbaha.115.305306"]}}