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Apolipoprotein A1 genotype affects the change in high density lipoprotein cholesterol subfractions with exercise training

      Abstract

      High density lipoprotein cholesterol (HDL-C) is a primary risk factor for cardiovascular disease. Apolipoprotein A-1 (apoA1) is the major HDL-associated apolipoprotein. The −75G/A single nucleotide polymorphism (SNP) in the apolipoprotein A1 gene (APOA1) promoter has been reported to be associated with HDL-C concentrations as well as HDL-C response to dietary changes in polyunsaturated fat intake. We examined the effect of this APOA1 SNP on exercise-induced changes in HDL subfraction distribution. From a cohort of healthy normolipidemic adults who volunteered for 6 months of supervised aerobic exercise, 75 subjects were genotyped for the −75G/A SNP. Of these, 53 subjects were G homozygotes (G/G) and 22 were A carriers (A/G and A/A). HDL subfractions were measured by nuclear magnetic resonance (NMR) spectroscopy by adding categories HDL-C 1 + 2 for the small subfraction, and HDL-C 3 + 4 + 5 for the large. The change in total HDL-C after exercise was 0.8 ± 7.2 mg/dL (+1.7%), and was not statistically significant. HDL subfraction amounts also did not significantly change with exercise training in the total cohort or in G homozygotes or A carriers. The amount of the large HDL subfraction increased in the G homozygotes and decreased in the A carriers (mean ± S.E.M., 1.8 ± 6.6 mg/dL versus −6.1 ± 2.3 mg/dL, p < 0.0005). In contrast, the amount of the small HDL subfraction decreased in G homozygotes and increased in A carriers (−1.3 ± 6.6 mg/dL versus 4.7 ± 1.2 mg/dL, p < 0.005). These results show that genetic variation at the APOA1 gene promoter is associated with HDL subfraction redistribution resulting from exercise training.

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      References

        • Barter P.
        • Kastelein J.
        • Nunn A.
        • Hobbs R.
        CN-FFEB: high density lipoproteins (HDLs) and atherosclerosis; the unanswered questions.
        Atherosclerosis. 2003; 168: 195-211
        • Brewer Jr., H.B.
        • Santamarina-Fojo S.
        Clinical significance of high-density lipoproteins and the development of atherosclerosis: focus on the role of the adenosine triphosphate-binding cassette protein A1 transporter.
        Am J Cardiol. 2003; 92: 10K-16K
        • Wilson P.W.
        • Abbott R.D.
        • Castelli W.P.
        High density lipoprotein cholesterol and mortality. The Framingham Heart Study.
        Arteriosclerosis. 1988; 8: 737-741
        • Freedman D.S.
        • Otvos J.D.
        • Jeyarajah E.J.
        • et al.
        Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease.
        Arterioscler Thromb Vasc Biol. 1998; 18: 1046-1053
        • Rosenson R.S.
        • Otvos J.D.
        • Freedman D.S.
        Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) Trial.
        Am J Cardiol. 2002; 90: 89-94
        • Decossin C.
        • Castro G.
        • Derudas B.
        • et al.
        Subclasses of LpA-I in coronary artery disease: distribution and cholesterol efflux ability.
        Eur J Clin Invest. 1997; 27: 299-307
        • Sich D.
        • Saidi Y.
        • Giral P.
        • et al.
        Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity.
        Metabolism. 1998; 47: 965-973
        • Asztalos B.
        • Lefevre M.
        • Wong L.
        • et al.
        Differential response to low-fat diet between low and normal HDL-cholesterol subjects.
        J Lipid Res. 2000; 41: 321-328
        • Kuller L.
        • Arnold A.
        • Tracy R.
        • et al.
        Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study.
        Arterioscler Thromb Vasc Biol. 2002; 22: 1175-1180
        • Ballantyne F.C.
        • Clark R.S.
        • Simpson H.S.
        • Ballantyne D.
        High density and low density lipoprotein subfractions in survivors of myocardial infarction and in control subjects.
        Metabolism. 1982; 31: 433-437
        • Pascot A.
        • Lemieux I.
        • Prud’homme D.
        • et al.
        Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity.
        J Lipid Res. 2001; 42: 2007-2014
        • Williams P.T.
        • Krauss R.M.
        • Vranizan K.M.
        • et al.
        Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women.
        Arterioscler Thromb. 1992; 12: 332-340
        • Otvos J.D.
        Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy.
        Clin Lab. 2002; 48: 171-180
        • Jeenah M.
        • Kessling A.
        • Miller N.
        • Humphries S.
        G to A substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI and high density lipoprotein cholesterol concentrations.
        Mol Biol Med. 1990; 7: 233-241
        • Sadaf A.
        • Siddiqui S.
        • Lestringant G.G.
        • Frossard P.M.
        Apolipoprotein AI promoter variant in blood pressure determination.
        Clin Genet. 2002; 61: 314-316
        • Lahoz C.
        • Pena R.
        • Mostaza J.M.
        • et al.
        CN-RSG: Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy.
        Atherosclerosis. 2003; 168: 289-295
        • Ordovas J.M.
        • Corella D.
        • Cupples L.A.
        • et al.
        Polyunsaturated fatty acids modulate the effects of the APOA1 G–A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: The Framingham Study.
        Am J Clin Nutr. 2002; 75: 38-46
        • Juo S.H.
        • Wyszynski D.F.
        • Beaty T.H.
        • Huang H.Y.
        • Bailey-Wilson J.E.
        Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis.
        Am J Med Genet. 1999; 82: 235-241
        • Barre D.E.
        • Guerra R.
        • Verstraete R.
        • et al.
        Genetic analysis of a polymorphism in the human apolipoprotein A-I gene promoter: effect on plasma HDL-cholesterol levels.
        J Lipid Res. 1994; 35: 1292-1296
      1. Seip RL, Otvos J, Bilbie C, et al. The effect of apolipoprotein E Genotype on serum lipoprotein particle response to exercise. Atherosclerosis (in press).

        • Thompson P.D.
        • Tsongalis G.J.
        • Seip R.L.
        • et al.
        Apolipoprotein e genotype and changes in serum lipids and maximal oxygen uptake with exercise training.
        Metabolism. 2004; 53: 193-202
        • Richard P.
        • Thomas G.
        • de Zulueta M.P.
        • et al.
        Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA.
        Clin Chem. 1994; 40: 24-29
        • Otvos J.D.
        • Jeyarajah E.J.
        • Bennett D.W.
        Quantification of plasma lipoproteins by proton nuclear magnetic resonance spectroscopy.
        Clin Chem. 1991; 37: 377-386
        • Durstine J.L.
        • Grandjean P.W.
        • Cox C.A.
        • Thompson P.D.
        Lipids, lipoproteins, and exercise.
        J Cardiopulm Rehabil. 2002; 22: 385-398
        • Kraus W.E.
        • Houmard J.A.
        • Duscha B.D.
        • et al.
        Effects of the amount and intensity of exercise on plasma lipoproteins.
        N Engl J Med. 2002; 347: 1483-1492
        • Thomas T.R.
        • Smith B.K.
        • Donahue O.M.
        • et al.
        Effects of omega-3 fatty acid supplementation and exercise on low-density lipoprotein and high-density lipoprotein subfractions.
        Metabolism. 2004; 53: 749-754
        • Wilund K.R.
        • Colvin P.L.
        • Phares D.
        • Goldberg A.P.
        • Hagberg J.M.
        The effect of endurance exercise training on plasma lipoprotein: AI and lipoprotein AI:AII concentrations in sedentary adults.
        Metabolism. 2002; 51: 1053-1060
        • Halle M.
        • Berg A.
        • Konig D.
        • Keul J.
        • Baumstark M.W.
        Differences in the concentration and composition of low-density lipoprotein subfraction particles between sedentary and trained hypercholesterolemic men.
        Metabolism. 1997; 46: 186-191
        • Frey I.
        • Baumstark M.W.
        • Berg A.
        Acute and delayed effects of prolonged exercise on serum lipoproteins. I. Composition and distribution of high density lipoprotein subfractions.
        Eur J Appl Physiol Occup Physiol. 1993; 66: 521-525
        • Krauss R.M.
        Triglycerides and atherogenic lipoproteins: rationale for lipid management.
        Am J Med. 1998; 105: 58S-62S
        • Gofman J.W.
        • Young W.
        • Tandy R.
        Ischemic heart disease, atherosclerosis, and longevity.
        Circulation. 1966; 34: 679-697
        • Knoblauch H.
        • Bauerfeind A.
        • Krahenbuhl C.
        • et al.
        Common haplotypes in five genes influence genetic variance of LDL and HDL cholesterol in the general population.
        Hum Mol Genet. 2002; 11: 1477-1485
        • Leon A.S.
        • Gaskill S.E.
        • Rice T.
        • et al.
        Variability in the response of HDL cholesterol to exercise training in the HERITAGE Family Study.
        Int J Sports Med. 2002; 23: 1-9
        • Halverstadt A.
        • Phares D.A.
        • Ferrell R.E.
        • et al.
        High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype.
        Metabolism. 2003; 52: 1505-1511
        • Herbert P.N.
        • Bernier D.N.
        • Cullinane E.M.
        • et al.
        High-density lipoprotein metabolism in runners and sedentary men.
        JAMA. 1984; 252: 1034-1037
        • Olchawa B.
        • Kingwell A.B.
        • Hoang A.
        • et al.
        Physical fitness and reverse cholesterol transport.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1087-1091
        • Jafari M.
        • Leaf D.A.
        • MacRae H.
        • et al.
        The effects of physical exercise on plasma prebeta-1 high-density lipoprotein.
        Metabolism. 2003; 52: 437-442
        • Williams P.T.
        The relationships of vigorous exercise, alcohol, and adiposity to low and high high-density lipoprotein-cholesterol levels.
        Metabolism. 2004; 53: 700-709
        • Sviridov D.
        • Kingwell B.
        • Hoang A.
        • Dart A.
        • Nestel P.
        Single session exercise stimulates formation of prebeta 1-HDL in leg muscle.
        J Lipid Res. 2003; 44: 522-526
        • Seip R.L.
        • Angelopoulos T.J.
        • Semenkovich C.F.
        Exercise induces lipoprotein lipase gene expression in skeletal muscle but not fat in sedentary adults.
        Amer J Physiol Endocrinol Metab. 1995; 268: E229-E236