Apolipoprotein A5 gene (APOA5) variability explains part of the individual's predisposition to hypertriacylglycerolaemia (HTG). Such predisposition has an inherited component (polymorphisms) and an acquired component regulated by the environment (epigenetic modifications). We hypothesize that the integrated analysis of both components will improve our capacity to estimate APOA5 contribution to HTG. We followed a recruit-by-genotype strategy to study a population composed of 44 individuals with high cardiovascular disease risk selected as being carriers of at least one APOA5 SNP (-1131T>C and/or, S19W and/or 724C>G) compared against 34 individuals wild-type (WT) for these SNPs. DNA methylation patterns of three APOA5 regions [promoter, exon 2 and CpG island (CGI) in exon 3] were evaluated using pyrosequencing technology. Carriers of APOA5 SNPs had an average of 57.5% higher circulating triacylglycerol (TG) levels (P=0.039). APOA5 promoter and exon 3 were hypermethylated whereas exon 2 was hypomethylated. Exon 3 methylation positively correlated with TG concentration (r=0.359, P=0.003) and with a lipoprotein profile associated with atherogenic dyslipidaemia. The highest TG concentrations were found in carriers of at least one SNP and with a methylation percentage in exon 3 ≥82% (P=0.009). In conclusion, CGI methylation in exon 3 of APOA5 acts, in combination with -1131T>C, S19W and 724C>G polymorphisms, in the individual's predisposition to high circulating TG levels. This serves as an example that combined analysis of SNPs and methylation applied to a larger set of genes would improve our understanding of predisposition to HTG.
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The effect on lung function and respiratory symptoms of reducing of consumption of conventional cigarettes by switching to electronic cigarettes is investigated by the Cibella et al. in their Clinical Science research article on pages 1929-1937 (volume 130, issue 21).
Research Article|
October 11 2016
APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels
Iris Oliva;
Iris Oliva
1
*Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació sanitària Pere Virgili (IISPV), CIBERDEM, 43201 Reus, Spain
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Montse Guardiola;
Montse Guardiola
1
*Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació sanitària Pere Virgili (IISPV), CIBERDEM, 43201 Reus, Spain
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Joan-Carles Vallvé;
Joan-Carles Vallvé
*Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació sanitària Pere Virgili (IISPV), CIBERDEM, 43201 Reus, Spain
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Daiana Ibarretxe;
Daiana Ibarretxe
*Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació sanitària Pere Virgili (IISPV), CIBERDEM, 43201 Reus, Spain
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Núria Plana;
Núria Plana
*Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació sanitària Pere Virgili (IISPV), CIBERDEM, 43201 Reus, Spain
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Lluís Masana;
Lluís Masana
*Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació sanitària Pere Virgili (IISPV), CIBERDEM, 43201 Reus, Spain
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David Monk;
David Monk
†Imprinting and Cancer Group, Epigenetics and Cancer Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), 08907 Barcelona, Spain
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Josep Ribalta
*Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació sanitària Pere Virgili (IISPV), CIBERDEM, 43201 Reus, Spain
Correspondence: Josep Ribalta (email [email protected])
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Publisher: Portland Press Ltd
Received:
June 09 2016
Revision Received:
July 21 2016
Accepted:
September 09 2016
Accepted Manuscript online:
September 09 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (22): 2053–2059.
Article history
Received:
June 09 2016
Revision Received:
July 21 2016
Accepted:
September 09 2016
Accepted Manuscript online:
September 09 2016
Citation
Iris Oliva, Montse Guardiola, Joan-Carles Vallvé, Daiana Ibarretxe, Núria Plana, Lluís Masana, David Monk, Josep Ribalta; APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels. Clin Sci (Lond) 1 November 2016; 130 (22): 2053–2059. doi: https://doi.org/10.1042/CS20160433
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