Scholarly Work - Health & Human Development

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Apolipoprotein A1 genotype affects the change in high density lipoprotein cholesterol subfractions with exercise training.
(2006-03) Ruaño, G.; Seip, R.L.; Windemuth, Andreas; Zöllner, S.; Tsongalis, Gregory J.; Otvos, J.; Ordovas, J.M.; Bilbie, C.; Miles, Mary; Zoeller, Robert F.; Visich, Paul S.; Gordon, P.M.; Angelopoulos, T.J.; Pescatello, Linda S.; Moyna, Niall M.; Thompson, P.D.
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 −75 G/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 −75 G/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.
Apolipoprotein E genotype and changes in serum lipids and maximal oxygen uptake with exercise training
(W.B. Saunders Co, 2004) Thompson, P.D.; Tsongalis, Gregory J.; Seip, R.L.; Bilbie, C.; Miles, Mary; Zoeller, Robert F.; Visich, Paul S.; Gordon, P.M.; Angelopoulos, T.J.; Pescatello, Linda S.; Bausserman, L.; Moyna, Niall M.
Physical activity improves lipid levels by altering triglyceride (TG) metabolism. Apolipoprotein E (Apo E) facilitates TG clearance by mediating lipoprotein binding to hepatic receptors, but Apo E also has less defined roles in skeletal muscle and nervous tissue. This study examined if variants in Apo E genotype affect the lipid and physiologic response to exercise training. Seven centers genetically screened 566 individuals to recruit 120 subjects into 6 gender-specific cohorts equal for the most common Apo E genotypes: E2/3, E3/3, and E3/4. Anthropometics, exercise capacity (Vo2max), serum lipids, and post heparin (PH) plasma lipase activities were measured before and after 6 months of supervised exercise training. Difference in the response (Δ) to training among the Apo E genotypes was the primary outcome variable. Differences in pretraining serum lipids among the Apo E genotypes mimicked those observed in population studies: TGs were slightly higher in E2/3 subjects, whereas low-density lipoprotein (LDL)-cholesterol (C) was lower (P = not significant [NS] ). TGs decreased 11% with training for the entire cohort (P < .0001) and 7%, 12%, and 14% for the Apo E 2/3, 3/3 and 3/4 groups, respectively (P = NS for Δ). LDL-C did not change in the entire cohort, but decreased slightly in the 2/3 and 3/3 subjects and increased 4% in the 3/4 group (P = NS for Δ). High-density lipoprotein (HDL)-C increased 2% for the entire cohort (P = .06) due to a 6% increase in the 3/3 group (P = .07 for Δ). Total cholesterol (TC)/HDL and LDL/HDL decreased with training in the 2/3 and 3/3 groups, but increased in the 3/4 subjects and these responses differed among the genotypes (P < .05 for Δ). Vo2max increased 9% to 10% for the entire cohort, but only 5% in the 3/3 subjects versus 13% in the 2/3 and 3/4 groups and these differences were significantly different among the genotypes (P < .01 for Δ). This is the first prospective study to demonstrate that the serum lipid response to exercise training differs by Apo E genotype in a pattern consistent with known metabolic differences among the variants. Surprisingly, Apo E genotype also affected the increase in aerobic capacity produced by exercise training possibly via undefined effects on nerve and skeletal muscle function.
Apolipoprotein E genotype and sex influence C-reactive protein levels regardless of exercise training status
(W.B. Saunders Co, 2008) Miles, Mary; Lowndes, J.; Sivo, S.; Seip, R.L.; Angelopoulos, T.J.
C-reactive protein (CRP) is a marker for systemic inflammation and increased cardiovascular disease risk. Regular exercise may decrease CRP. Apolipoprotein E (apo E) has 3 common genotype variants—E2/3, 3/3, and 3/4—that modulate lipid metabolism and may have other metabolic physiologic roles, including some evidence that the genotype affects CRP levels. We assessed fasting serum CRP in 117 (male = 51, female = 66) healthy adults who volunteered for a 6-month aerobic exercise program. Both pre- and posttraining measurements were available in 71 (male = 31, female = 40) subjects. At baseline and follow-up, the numbers of subjects in the 3 groups were approximately equal: 2/3, n = 33 and 20; 3/3, n = 41 and 26; and 3/4, n = 43 and 25. At baseline, CRP levels differed by apo E genotype: means ± SD were 2.84 ± 2.18, 2.59 ± 2.34, and 1.90 ± 2.13 mg/L for E2/3, 3/3, and 3/4 subjects, respectively (3/4 vs 2/3, P b .05). In women, CRP was higher than that in men (3.14 ± 2.49 vs 2.12 ± 2.13 mg/L, P b .006). Exercise failed to affect CRP in the entire cohort (2.68 ± 2.38 vs 2.52 ± 2.48 mg/L) or in any apo E genotype group, and the apo E genotype effect observed at baseline persisted after training. In a largely white study cohort, CRP is higher in apo E3/3 than in 3/4 subjects and in women compared with men, but remains unchanged by 6 months of standard aerobic exercise training of the volume and higher intensity promoted by national organizations to reduce cardiovascular disease risk. How apo E genotype affects CRP is not known.
Interactive Effects of APOE Haplotype, Sex, and Exercise on Postheparin Plasma Lipase Activities
(American Physiological Society, 2011) Miles, Mary; Seip, R.L.; Zoeller, Robert F.; Angelopoulos, T.J.; Salonia, J.; Bilbie, C.; Moyna, Niall M.; Visich, Paul S.; Pescatello, Linda S.; Gordon, P.M.; Tsongalis, Gregory J.; Bausserman, L.; Thompson, P.D.
Hepatic lipase (HL) and lipoprotein lipase (LPL) activities (HLA, LPLA) modify lipoproteins and facilitate their binding to hepatic receptors. Apolipoprotein E (APOE) physically interacts with the lipases, and the three common haplotypes of the APOE gene (ε2, ε3, and ε4) yield protein isoforms (E2, E3, and E4, respectively) that are functionally different. Lipase activities themselves differ by sex and exercise training status. The interaction of APOE genotype, exercise training, and sex effects on lipase activities has not been studied. We measured postheparin plasma lipase activities in normolipidemic men and women with the three most common APOE genotypes, which are the haplotype combinations ε2/ε3 (n 53 ), ε3/ε3 (n 62), and ε4/ε3 (n 52), enrolled in 6 mo of aerobic exercise training. These haplotype combinations comprise an estimated 11.6, 62.3, and 21.3% of the population, respectively. Baseline HLA was 35% lower in women than in men (P 0.0001). In men but not women, HLA was higher in ε2/ε3 group compared with ε4/ε3 (P 0.01) and ε3/ε3 (P 0.05). Neither sex nor APOE genotype affected baseline LPLA. Training decreased HLA by 5.2% (P 0.018) with no APOE effect. The apparent increase in LPLA following exercise was significant and APOE dependent only when corrected for baseline insulin (P 0.05). Exercise decreased LPLA by 0.8 mol free fatty acid (FFA)·ml 1·h 1 ( 6%) in ε3/ε3 compared with the combined increases of 6.6% in ε2/ε3 and 12% in ε4/ε3 (P 0.018 vs. ε3/ε3). However, these differences were statistically significant only after correcting for baseline insulin. We conclude that common APOE genotypes interact with 1) sex to modulate HLA regardless of training status, with ε2/ε3 men demonstrating higher HLA than ε3/ε3 or ε4/ε3 men, and 2) aerobic training to modulate LPLA, regardless of sex, with ε3/ε3 subjects showing a significant decrease compared with an increase in ε2/ε3 and ε3/ε4 after controlling for baseline insulin.