Atherosclerosis 191 (2007) 409–417 The -1131 T > C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study Nicola Martinelli a , Elisabetta Trabetti b , Antonella Bassi c , Domenico Girelli a , Simonetta Friso a , Francesca Pizzolo a , Marco Sandri a , Giovanni Malerba b , Pier Franco Pignatti b , Roberto Corrocher a , Oliviero Olivieri a,∗ a University of Verona, Department of Clinical and Experimental Medicine, Italy b University of Verona, Section of Biology and Genetics, Department of Mother and Child and Biology-Genetics, Italy c University of Verona, Institute of Clinical Chemistry, Italy Received 3 February 2006; received in revised form 17 March 2006; accepted 4 April 2006 Available online 8 May 2006 Abstract High plasma concentrations of triglycerides (TG) and apolipoprotein C-III (ApoC-III) are well-known risk factors for cardiovascular disease. Two variants of the recently discovered APOA5, 1131 C>T and S19W, have been associated with hypertriglyceridemia, whereas their relation with coronary artery disease (CAD) remains controversial. Nine hundred and thirteen angiografically defined patients (669 CAD and 244 CAD-free) were genotyped for APOA5 -1131 C > T and S19W polymorphisms. Carriership of the APOA5 -1131 C allele was identified, by multiple linear regression models, as a significant independent predictor for both TG (standardized -coefficient = 0.112; p = 0.010) and ApoC-III variability (standardized -coefficient = 0.113; p = 0.013). Similarly, APOA5 19W allele carriership was a significant independent predictor for both TG (standardized -coefficient = 0.113; p = 0.007) and ApoC- III variability (standardized -coefficient = 0.088; p = 0.045). Despite the association with at-risk lipid profile, no significant difference was detected in the distribution of both APOA5 gene polymorphisms between subjects with or without CAD. Moreover, homozygous carriers of the APOC3 -455 C, another TG- and ApoC-III raising variant, showed a significant increased risk for CAD (OR 1.90 with 95% CI 1.002–3.62; p = 0.049; by multiple logistic regression). Different genotypes, i.e., APOA5 and APOC3 variants, may lead to similar biochemical phenotypes, namely hypertriglyceridemia, but to contrasting clinical phenotypes such as the presence of angiographically proven CAD. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: APOA5 polymorphisms; Triglycerides; Apolipoprotein C-III; Coronary artery disease 1. Introduction High plasma triglyceride (TG) levels are a well-reco- gnized risk factor for cardiovascular disease [1]. TG levels are strongly influenced by genetic factors, although heritability ∗ Corresponding author at: Department of Clinical and Experimental Medicine, University of Verona School of Medicine, Policlinico G.B. Rossi 37134 Verona, Italy. Tel.: +39 045 580111; fax: +39 045 580111. E-mail address: oliviero.olivieri@univr.it (O. Olivieri). has been observed to vary widely (20–80%) in different stud- ies [2]. Apolipoprotein gene cluster APOA1/C3/A4/A5 on chromosome 11q23 plays a pivotal role in TG metabolism [3] and the recently discovered APOA5 gene has gained attention as a key regulator of TG levels [4]. This gene is exclusively expressed in liver and its product, ApoA-V, is secreted in plasma, where it is associated with high-density lipoproteins (HDL), very low density lipoproteins (VLDL), chylomicrons, but not with low density lipoproteins (LDL) [5,6]. ApoA-V apolipoprotein is not abundant in plasma since its concentra- 0021-9150/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2006.04.009