A twin study of heritability of plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity

Lenzini, Livia; Antezza, Katia; Caroccia, Brasilina; Wolfert, Robert L.; Szczęch, Radosław; Cesari, Maurizio; Williams, Christopher J.; Rossi, Gian Paolo

doi:10.1016/j.atherosclerosis.2008.08.045

Cited by 13 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Measurements were performed by diaDexus Inc. (South San Francisco, CA). 17 Lp-PLA 2 mass was measured with a sandwich enzyme immunoassay (PLAC™ Test; diaDexus). Lp-PLA 2 activity was measured by an enzymatic assay using a tritium-labeled platelet activating factor (PAF) analog as the substrate.…”

Section: Methodsmentioning

confidence: 99%

Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: The multi ethnic study of atherosclerosis

et al. 2015

View full text Add to dashboard Cite

Objective Prospective studies reporting a positive association of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with incident cardiovascular disease (CVD) have included primarily white individuals. We evaluated associations of Lp-PLA2 and first-time cardiovascular events in a healthy multi-ethnic cohort characterized by presence or absence of baseline subclinical atherosclerosis. Methods Lp-PLA2 mass and activity were measured at baseline in 5456 participants in the Multi-Ethnic Study of Atherosclerosis. Individuals were characterized for presence of baseline subclinical disease (coronary artery calcium score>0 or carotid intima-media thickness value>80th percentile) and followed prospectively for development of CVD events (coronary heart disease, ischemic stroke, and cardiovascular death). Results 516 incident CVD events occurred over median follow-up of 10.2 years. In adjusted Cox proportional hazards models, each higher standard deviation of both Lp-PLA2 activity and mass was associated with an increased risk of cardiovascular events; hazard ratios (HR; 95% confidence intervals (CI)) 1.12 (1.01–1.26) for Lp-PLA2 activity and 1.10 (1.01–1.21) for mass. Associations did not differ by subclinical disease status (p-value for interaction 0.99 for Lp-PLA2 activity and 0.32 for Lp-PLA2 mass) and there was no confounding by subclinical atherosclerosis measures. Associations of Lp-PLA2 activity but not mass were weaker in Chinese participants but there were relatively few events among Chinese in race-stratified analysis. Conclusion In this multi-ethnic cohort, Lp-PLA2 was positively associated with CVD risk, regardless of the presence of coronary artery calcium or a thickened carotid-intimal media.

show abstract

Section: Methodsmentioning

confidence: 99%

Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: The multi ethnic study of atherosclerosis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Two other polymorphisms A379V and rs13210554 were not linked to change in Lp PLA 2 activity, but the latter (located in the PLA 2 G7 promoter region) was more prevalent in cases with myocardial infarction than in controls (P ¼ 0.039). Further insight into the genetics of Lp PLA 2 was provided by Lenzini et al [35], who examined Lp PLA 2 mass and activity in 54 healthy twins and estimated heritability for mass at 0.37 (P ¼ 0.11) and for activity at 0.54 (P ¼ 0.066).…”

Section: Pathophysiology and Genetics Of Lipoproteinassociated Phosphmentioning

confidence: 99%

Lipoprotein-associated phospholipase A2 as a biomarker of coronary heart disease and a therapeutic target

Packard

2009

Current Opinion in Cardiology

View full text Add to dashboard Cite

show abstract

“…Most recently, a study in monozygotic and dizygotic twins of Caucasian origin was conducted, to investigate the heritability of plasma levels (mass) and activity of Lp-PLA 2 [30]. The authors reported that when phenotypic covariance was partitioned into additive genetic effects, environmental effects common to co-twins, and error variance components, a non-negligible component of both Lp-PLA 2 mass and activity was accounted for by genetic effects, suggesting that both Lp-PLA 2 activity and mass variance may be genetically determined, although the heritability estimates were only significant for Lp-PLA 2 activity.…”

Section: Biochemistry and Biologymentioning

confidence: 99%

Lp-PLA2 Inhibition—The Atherosclerosis Panacea?

Karakas

Köenig

2010

Pharmaceuticals

View full text Add to dashboard Cite

Based on the complex pathophysiology of atherosclerosis, a large number of biomarkers that relate to lipids, inflammation, immunity, thrombosis and hemostasis, have been investigated experimentally, in epidemiologic studies and in clinical trials. Interest focuses on their potential role to aid in risk stratification, as possible surrogate markers of atherosclerosis, and potential targets for therapy. More recently, one lipid associated biomarker, lipoprotein-associated phospholipase A2 (Lp-PLA2), has gained considerable interest. In addition to a plausible pathophysiological role by generating pro-inflammatory and pro-atherogenic compounds from oxidized LDL in the vessel wall, there is a large, fairly consistent epidemiological database indicating that increased levels of Lp-PLA2 mass or activity are associated with increased risk for cardiovascular outcomes; such data further suggest that it might improve risk stratification. In addition, clinical studies indicate that increased Lp-PLA2 levels are associated with endothelial dysfunction. Moreover, it may also serve as an interesting therapeutic target, since a specific inhibitor of the enzyme is available with promising animal data and initial positive data in humans. Recent experimental data from a hyperlipidemic diabetic pig model strongly suggest that increased Lp-PLA2 in the vessel wall is associated with a more vulnerable plaque phenotype which can be modulated by inhibiting Lp-PLA2 activity. A biomarker study in more than 1,000 patients with CHD over three months has demonstrated a positive effect on various inflammatory molecules. In addition, an imaging study using IVUS based modalities (greyscale, virtual histology, and palpography) together with a panel of biomarkers (IBIS-2) has been done in more than 300 patients with CHD treated over 12 months and results indicate that the progression of the necrotic core of the plaque can be retarded. Inhibition of the pro-atherogenic and pro-inflammatory effects of Lp-PLA2 may therefore contribute to decrease the residual risk in high risk patients already on polypharmacotherapy. This hypothesis is now being tested in two large phase 3 clinical trials. Thus, Lp-PLA2 indeed may represent a biomarker and a promising target for intervention.

show abstract

A twin study of heritability of plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity

Cited by 13 publications

References 30 publications

Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: The multi ethnic study of atherosclerosis

Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: The multi ethnic study of atherosclerosis

Lipoprotein-associated phospholipase A2 as a biomarker of coronary heart disease and a therapeutic target

Lp-PLA2 Inhibition—The Atherosclerosis Panacea?

Contact Info

Product

Resources

About