4.7 Heritability of Plasma Lipoprotein-Associated Phospholipase A2 (Lp-PLA2): a New Marker of Cardiovascular Risk
- PDF / 46,572 Bytes
- 1 Pages / 592.441 x 751.181 pts Page_size
- 85 Downloads / 171 Views
High Blood Press Cardiovasc Prev 2008; 15 (3): 171-215 1120-9879/08/0003-0171/$48.00/0 © 2008 Adis Data Information BV. All rights reserved.
Genetics and Pharmacogenomics 4.7 Heritability of Plasma Lipoprotein-Associated Phospholipase A2 (Lp-PLA2): a New Marker of Cardiovascular Risk L. Lenzini (1), B. Caroccia (1), K. Antezza (1), R. Wolfert (2), R. Szczech (3), M. Cesari (1), K. Narkiewicz (3), C. Williams (4), G. Rossi (1) ` di Padova, Padova, Italy, (2)DiaDexus, San Francisco USA, (1)Universita (3)University of Gdansk, Gdansk, Poland, (4)University of Idaho, Moscow, Idaho, USA Introduction. Lipoprotein-associated phospholipase A2 (Lp-PLA2 ), is involved in degradation of platelet-activating factor (PAF) and phospholipids associated with LDL, and in production of lysophosphatidylcholine (lysoPC) and oxidized non-esterified fatty acids (NEFA) that have proinflammatory properties. Hence, the function of Lp-PLA2 in the atherosclerotic process is controversial: the degradation of pro-inflammatory phospholipids in LDL would suggest anti-atherogenic properties, while the production of pro-inflammatory species (lysoPC and NEFA) would support a pro-atherogenic role. However, the determinants of plasma Lp-PLA2 are unknown. Aim. To verify whether the Lp-PLA2 plasma levels are genetically determined. Methods. 54 healthy twins’ pairs were enrolled. The levels (mass) and activity of Lp-PLA2 were measured in DiaDexus (USA) laboratories, with an inter-assay coefficient of variability equal to 3% (mass) and 2% (activity). We estimated genetic variance and heritability of Lp-PLA2 mass and activity with variance and path analyses. We determined intra-class-correlation (ICC) and proportion of additive genetic variance from a model comprising additive genetic influence (A), environmental effect common to co-twins (C) and individually unique environmental (E) influence (ACE) model. Twins were genotyped at PLA2G7 gene functional single nucleotide polymorphisms (SNPs): Thr198Ile (exon 7), His92Arg (exon 4) and Ala 379Val (exon 9). Zygosity was assessed with highly discriminating VNTR (variable number of tandem repeats) micro- and mini-satellite systems were analyzed, by PCR and gel electrophoresis. Results. 26 twin pairs were monozygotic (MZ) and 28 dizygotic (DZ). The mean Lp-PLA2 mass and activity were correlated (r=0.87, p
Data Loading...
