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Published in: Diabetologia 10/2006

01-10-2006 | Short Communication

The apolipoprotein A-V genotype and plasma apolipoprotein A-V and triglyceride levels: prospective risk of type 2 diabetes. Results from the Northwick Park Heart Study II

Authors: P. J. Talmud, J. A. Cooper, H. Hattori, I. P. Miller, G. J. Miller, S. E. Humphries

Published in: Diabetologia | Issue 10/2006

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Abstract

Aims/hypothesis

We sought to establish the relationship between plasma apolipoprotein A-V (APOA5, previously known as apoA-V) and triglyceride levels and to determine the impact of the APOA5 genotype on APOA5 levels and development of type 2 diabetes in a 15-year follow-up study of healthy UK men.

Materials and methods

APOA5 −1131T>C and S19W genotypes were determined in 2,490 men, of whom 145 subsequently developed type 2 diabetes. In a subset of 299 men, we also determined APOA5 levels.

Results

Plasma APOA5 levels positively correlated with triglycerides (r=0.18, p<0.002) and were not different in men who subsequently developed type 2 diabetes compared with healthy men (p=0.7). Carriers of either APOA5 W19 or −1131C had, as expected, higher plasma triglycerides. However, while W19 carriers had significantly higher APOA5 levels (p=0.0003), APOA5 levels were not associated with −1131T>C (p=0.63), reinforcing the idea that the reported −1131C association with triglycerides levels is due to linkage disequilibrium with variants in the APOC3 gene, and not due to the direct effect on APOA5 levels. Overall no effect of APOA5 −1131T>C or S19W was found on type 2 diabetes risk.

Conclusions/interpretation

In contrast to animal studies, in man, plasma APOA5 positively correlates with plasma triglyceride levels. In prospective analysis, with the caveat that numbers were small, APOA5 genotypes do not appear to have an impact on risk of development of type 2 diabetes.
Literature
1.
go back to reference Pennacchio LA, Olivier M, Hubacek JA et al (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173PubMedCrossRef Pennacchio LA, Olivier M, Hubacek JA et al (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173PubMedCrossRef
2.
go back to reference Pennacchio LA, Olivier M, Hubacek J, Krauss RM, Rubin EM, Cohen JC (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Gen 11:3031–3038PubMedCrossRef Pennacchio LA, Olivier M, Hubacek J, Krauss RM, Rubin EM, Cohen JC (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Gen 11:3031–3038PubMedCrossRef
3.
go back to reference Talmud PJ, Hawe E, Martin S et al (2002) Relative contribution of variation within the APOC3-A4-A5 gene cluster in determining plasma triglycerides. Hum Mol Gen 11:3039–3046PubMedCrossRef Talmud PJ, Hawe E, Martin S et al (2002) Relative contribution of variation within the APOC3-A4-A5 gene cluster in determining plasma triglycerides. Hum Mol Gen 11:3039–3046PubMedCrossRef
4.
go back to reference Olivier M, Wang X, Cole R et al (2004) Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11. Genomics 83:912–923PubMedCrossRef Olivier M, Wang X, Cole R et al (2004) Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11. Genomics 83:912–923PubMedCrossRef
5.
go back to reference Miller GJ, Bauer KA, Barzegar S, Cooper JA, Rosenberg RD (1996) Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease. Thromb Haemost 75:767–771PubMed Miller GJ, Bauer KA, Barzegar S, Cooper JA, Rosenberg RD (1996) Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease. Thromb Haemost 75:767–771PubMed
6.
go back to reference Gable DR, Stephens JW, Cooper JA, Miller GJ, Humphries SE (2005) Variation in the UCP2-UCP3 gene cluster predicts the development of type 2 diabetes in the Northwick Park Heart study II. Diabetes 55:1504–1511CrossRef Gable DR, Stephens JW, Cooper JA, Miller GJ, Humphries SE (2005) Variation in the UCP2-UCP3 gene cluster predicts the development of type 2 diabetes in the Northwick Park Heart study II. Diabetes 55:1504–1511CrossRef
7.
go back to reference Ishihara M, Kujiraoka T, Iwasaki T et al (2005) A sandwich enzyme-linked immunosorbent assay for human plasma apolipoprotein A-V concentration. J Lipid Res 46:2015–2022PubMedCrossRef Ishihara M, Kujiraoka T, Iwasaki T et al (2005) A sandwich enzyme-linked immunosorbent assay for human plasma apolipoprotein A-V concentration. J Lipid Res 46:2015–2022PubMedCrossRef
8.
go back to reference Merkel M, Heeren J (2005) Give me A5 for lipoprotein hydrolysis! J Clin Invest 115:2694–2696CrossRef Merkel M, Heeren J (2005) Give me A5 for lipoprotein hydrolysis! J Clin Invest 115:2694–2696CrossRef
9.
go back to reference Talmud PJ, Palmen J, Putt W, Lins L, Humphries SE (2005) Determination of the functionality of common APOA5 polymorphisms. J Biol Chem 280:28215–28220PubMedCrossRef Talmud PJ, Palmen J, Putt W, Lins L, Humphries SE (2005) Determination of the functionality of common APOA5 polymorphisms. J Biol Chem 280:28215–28220PubMedCrossRef
10.
go back to reference Talmud PJ, Martin S, Taskinen MR et al (2004) APOA5 gene variants, lipoprotein particle distribution and progression of coronary heart disease: results from the LOCAT study. J Lipid Res 45:750–756PubMedCrossRef Talmud PJ, Martin S, Taskinen MR et al (2004) APOA5 gene variants, lipoprotein particle distribution and progression of coronary heart disease: results from the LOCAT study. J Lipid Res 45:750–756PubMedCrossRef
11.
go back to reference van Dijk KW, Rensen PC, Voshol PJ, Havekes LM (2004) The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism? Curr Opin Lipidol 15:239–246PubMedCrossRef van Dijk KW, Rensen PC, Voshol PJ, Havekes LM (2004) The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism? Curr Opin Lipidol 15:239–246PubMedCrossRef
Metadata
Title
The apolipoprotein A-V genotype and plasma apolipoprotein A-V and triglyceride levels: prospective risk of type 2 diabetes. Results from the Northwick Park Heart Study II
Authors
P. J. Talmud
J. A. Cooper
H. Hattori
I. P. Miller
G. J. Miller
S. E. Humphries
Publication date
01-10-2006
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2006
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0387-0

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