Abstract
The −1131T>C polymorphism in the newly identified apolipoprotein A5 (APOA5) gene has been associated with elevated plasma triglycerides. We determined its incidence in 915 patients attending a lipid outpatient clinic. The frequency of the C allele was significantly higher in patients with triglycerides above the 90th percentile and patients with type III hyperlipidemia compared to those with hypercholesterolemia. The C allele was associated with increased plasma triglycerides and decreased plasma HDL cholesterol, conditions associated with an increased risk of coronary heart disease. The effects on plasma lipids were only observed in overweight (BMI>25) patients and were greater in patients who were also carriers of a least one ε4 allele in the APOE gene. Thus additional genetic and/or metabolic factors are required in order for the triglyceride raising and HDL lowering effect of the −1131T>C polymorphism in APOA5 to be expressed.
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Abbreviations
- APO :
-
Apolipoprotein
- BMI :
-
Body mass index
- DM 2 :
-
Diabetes mellitus type 2
- HDL :
-
High-density lipoprotein
- HLP :
-
Hyperlipidemia
- LPL :
-
Lipoprotein lipase
- SNP :
-
Single nucleotide polymorphism
References
Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219
Breslow JL (2000) Genetics of lipoprotein abnormalities associated with coronary heart disease susceptibility. Annu Rev Genet 34:233–254
Talmud PJ (2001) Genetic determinants of plasma triglycerides: impact of rare and common mutations. Curr Atheroscl Re 3:191–199
Fisher RM, Mailly F, Peacock RE, Hamsten A, Seed M, Yudkin JS, Beisiegel U, Feussner G, Miller G, Humphries SE, Talmud PJ (1995) Interaction of the lipoprotein lipase asparagine 291→serine mutation with body mass index determines elevated plasma tricylglycerol concentrations: a study in hyperlipidemic subjects, myocardial infarction survivors, and healthy adults. J Lipid Res 36:2104–2112
Wittrup HH, Nordestgaard BG, Steffensen R, Jensen G, Tybjaerg-Hansen A (2002) Effect of gender on phenotypic expression of the S447X mutation in LPL. The Copenhagen City Heart Study. Atherosclerosis 165:119–126
Pennacchio LA, Oliver M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, Krauss RM, Rubin EM (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294 ;169–73
van der Vliet HN, Sammels MG, Leegwater ACJ, Levels JHM, Reitma PH, Boers W, Chamuleau RAFM (2001) Apolipoprotein A-V. A novel apolipoprotein associated with an early phase of liver regeneration. J Biol Chem 276:44512–44520
Vliet HN van der, Schaap FG, Levels JHM, Ottenhoff R, Looije N, Wesseling JG, Groen AK, Chamuleau RAFM (2002) Adenoviral over expression of apolipoprotein A-V reduces serum levels of triglycerides and cholesterol in mice. Biochem Biophys Res Commun 295:1156–1159
Pennacchio LA, Oliver M, Hubacek JA, Krauss RM, Rubin EM, Cohen JC (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 11:3031–3038
Talmud P, Hawe E, Martin S, Oliver M, Miller GJ, Rubin EM, Pennacchio LA, Humphries SE (2002) Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet 11:3039–3046
Ribalta J, Figuera L, Fernández-Ballart J, Vilella E, Cabezas MC, Masana L, Joven J (2002) Newly identified apolipoprotein AV gene predisposes to high plasma triglycerides in familial combined hyperlipidemia. Clin Chem 48:1597–1600
Nabika T, Nasreen S, Kobayashi S, Masuda J (2002) The genetic effect of the apoprotein AV gene on serum triglyceride level in Japanese. Atherosclerosis 165:201–204
Endo K, Yanagi H, Araki J, Hirano C, Yamakawa-Koybayashi K, Tomura S (2002) Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren. Hum Genet 111:570–572
Mahley RW, Huang Y, Rall SC (1999) Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes. J Lipid Res 40:1933–1949
Mailly F, Tugrul Y, Reymer PWA, Bruin T, Seed M, Groenemeyer BF, Asplund-Carlson A, Vallance D, Winder AF, Miller GJ, Kastelein JJP, Hamsten A, Olivecrona G, Humphries SE, Talmud P (1995). A common variant in the gene for lipoprotein lipase (Asp9→Asn): functional implications and prevalence in normal and hyperlipidemic subjects. Arterioscler Thromb Vasc Biol 15:468–478
Zhang H, Reymer PWA, Liu MS, Forsythe IJ, Groenemeyer BE, Frohlich J, Brunzell JD, Kastelein JJP, Hayden MR, Ma Y (1995) Patients with apoE3 deficiency (E2/2, E3/2, and E4/2) who manifest with hyperlipidemia have increased frequency of an Asn291→Ser mutation in the human LPL gene. Arterioscler Thromb Vasc Biol 15:1695–1703
Hata A, Robertson M, Emi M, Lalouel JM (1990) Direct detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene. Nucleic Acid Res 18:5407–5410
Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with Hha I. J Lipid Res 31:545–548
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We thank Edda George for excellent technical assistance.
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Evans, D., Buchwald, A. & Beil, F.U. The single nucleotide polymorphism −1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipidemia. J Mol Med 81, 645–654 (2003). https://doi.org/10.1007/s00109-003-0465-4
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DOI: https://doi.org/10.1007/s00109-003-0465-4