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1.  APOE Genotype Affects Black-White Responses of High-Density Lipoprotein Cholesterol Subspecies to Aerobic Exercise Training 
Metabolism: clinical and experimental  2008;57(12):1669-1676.
To determine whether ethnicity interacts with the APO E genotype to influence conventionally-measured high density lipoprotein cholesterol (HDL-C) subfraction levels and Nuclear Magnetic Resonance measured (HDLNMR-C) particle size at baseline, after training, and changes with training.
After a 6-week dietary stabilization period, men and postmenopausal women 50-75 yrs old underwent baseline testing (NMR lipid, VO2max, body composition, and genotyping assessments). Tests were repeated after completing 24 wks of endurance exercise-training.
At baseline, APO E2/3 Blacks had significantly larger particle size (P<0.001) and higher total HDLNMR-C particle concentration (P=0.006) than Whites. After 6 months of endurance exercise-training, APO E2/3 Blacks maintained a significantly larger HDLNMR-C particle size (P<0.001), and particle concentration of the large HDLNMR-C than APO E2/3 Whites (P<0.001). In multivariate ANOVAs adjusted for demographic and environmental confounding factors, and training-induced changes in lean body mass and intra-abdominal fat; the model explained ∼33 percent of the observed variability in training-induced improvements in HDLNMR-C particle size (P=0.002), with APO E2/3 Blacks having a greater increase in training-induced changes in HDLNMR-C particle size. In a separate but similarly adjusted model for conventionally-measured HDL2-C, the model explained, ∼49 percent of the observed variability in training-induced changes in HDL2-C.
Ethnicity interacted with the E2/3 genotype at the APO E gene locus to influence higher baseline, after training, and greater exercise training-induced improvements in the advantageous HDL-C subfractions in Blacks than in Whites. APO E2/3 Blacks may benefit more from aerobic-fitness to reduce CVD risk.
PMCID: PMC2631415  PMID: 19013289
Cholesterol; Genetics; Ethnicity; Exercise
2.  Variation in the Lectin-like Oxidized LDL Receptor 1 (LOX-1) Gene Is Associated With Plasma Soluble LOX-1 Levels 
Experimental physiology  2008;93(9):1085-1090.
The lectin-like ox-LDL receptor 1 (LOX-1) expressed on vascular cells plays a major role in atherogenesis by internalizing and degrading oxidized LDL. LOX-1 can be cleaved from the cell surface and released as soluble LOX-1 (sLOX-1), and elevated sLOX-1 levels may be indicative of atherosclerotic plaque instability. We examined associations between the LOX-1 3′UTR-C/T and G501C polymorphisms and plasma sLOX-1 levels in 97 healthy older men and women. The frequencies for the 3′UTR-T and 501C alleles were 46% and 10%, respectively. Plasma sLOX-1 levels were significantly higher in the 3′UTR CC genotype group compared to both the CT (p=0.02) and TT (p=0.002) genotype groups. Plasma sLOX-1 were also significantly higher in the 501GC genotype group compared to the GG genotype group (p=0.004). In univariate analyses, sLOX-1 levels were significantly associated with both the 3′UTR-C/T and G501 C polymorphisms. These associations remained significant after adjusting for age, gender, race, and BMI. In conclusion, variation in the LOX-1 gene is associated with plasma sLOX-1 levels in older men and women.
PMCID: PMC2652129  PMID: 18469066
receptor; cardiovascular; gene expression
3.  Differential aerobic exercise-induced changes in plasma aldosterone between African Americans and Caucasians 
Experimental physiology  2007;92(5):871-879.
Aldosterone influences the kidney’s regulation of blood pressure (BP), but aldosterone can contribute to the pathogenesis of hypertension. Blood pressure is reduced with aerobic exercise training (AEX), but the extent to which plasma aldosterone (PA) levels change is unclear. The purpose of this study was to determine whether 6 months of AEX changed PA levels, 24 h sodium (Na+) excretion and BP in prehypertensive and hypertensive subjects and whether these changes differed according to ethnicity. The study was performed in the Kinesiology Department at the University of Maryland, College Park, and 35 (22 Caucasian; 13 African American) sedentary prehypertensive and hypertensive subjects completed 6 months of AEX. Blood samples were collected under fasting and supine conditions, and PA was measured by radioimmunoassay. In total population aerobic exercise training increased maximal oxygen consumption (24 ± 0.8 versus 28 ± 1 ml kg−1 min−1, P < 0.001) and decreased PA levels (97 ± 11 versus 72 ± 6 pg ml−1, P = 0.01), body mass index (28 ± 0.5 versus 28 ± 0.5 kg m−2, P = 0.004) and weight (85 ± 2 versus 83 ± 2 kg, P = 0.003). Aerobic exercise training decreased PA levels (from 119 ± 16 to 81 ± 7 pg ml−1, P = 0.02) in the Caucasians but there was no change in BP or Na+ excretion. African American participants had no significant changes in PA levels, BP and Na+ excretion. Plasma aldosterone levels were 47% lower at baseline (P = 0.01) and 30% lower after AEX (P = 0.04) in African American participants compared with Caucasians. Baseline (P = 0.08) and final PA levels (P = 0.17) did not differ between the two groups after accounting for baseline and final intra-abdominal fat, respectively. The reduction in PA levels with AEX appeared to be driven by the change in PA levels in Caucasian participants. Fat distribution contributed to the ethnic differences in PA levels.
PMCID: PMC2729146  PMID: 17483200
4.  Elevated Soluble Lectin-like Oxidized LDL Receptor 1 (LOX-1) Levels in Obese Postmenopausal Women 
Obesity (Silver Spring, Md.)  2008;16(6):1454-1456.
We investigated the association between soluble lectin-like oxidized LDL receptor 1 (sLOX-1) levels and obesity in older women. Fifty-one (10 lean, 22 overweight, and 19 obese) postmenopausal women were included in this small retrospective analysis. Plasma sLOX-1 levels were measured using a chemiluminescent ELISA. Plasma levels of sLOX-1 were significantly higher in obese women (55.33±4.49 pg/mL) compared to lean (30.91±6.19 pg/mL, p=0.002) and overweight women (38.31±4.18 pg/mL, p=0.017). Plasma sLOX-1 levels were positively associated with body weight, BMI, total body fat, and trunk fat. The relationship between sLOX-1 and BMI was attenuated after adjustment for age, HRT, and body fat. In conclusion, obese women have higher sLOX-1 levels, which may reflect increased LOX-1 expression in adipose tissue.
PMCID: PMC2677801  PMID: 18388896
obesity; postmenopausal women; receptors
5.  C-Reactive Protein Genotypes Affect Baseline, but not Exercise Training–Induced Changes, in C-Reactive Protein Levels 
The goal of this study is to determine whether C-reactive protein (CRP) gene variants affect baseline and training-induced changes in plasma CRP levels.
Methods and Results
Sixty-three sedentary men and women aged 50 to 75 years old underwent baseline testing (VOmax, body composition, CRP levels). They repeated these tests after 24 weeks of exercise training while on a low-fat diet. The CRP +219G/A variant significantly associated with CRP levels before and after training after accounting for the effects of demographic and biological variables. CRP −732A/G genotype was significantly related on a univariate basis to CRP levels after training. The CRP +29T/A variant did not affect CRP levels before or after training. In regression analyses, the +219 and −732 variants each had significant effects on CRP levels before and after training. Subjects homozygous for the common A/G −732/+219 haplotype exhibited the highest CRP levels, and having the rare allele at either site was associated with significantly lower CRP levels. CRP levels decreased significantly with training (−0.38±0.18 mg/L; P=0.03). However, none of the CRP variants was associated with the training-induced CRP changes.
CRP +219G/A and −732A/G genotypes and haplotypes and exercise training appear to modulate CRP levels. However, training-induced CRP reductions appear to be independent of genotype at these loci.
PMCID: PMC2643022  PMID: 15271790
C-reactive protein; genetics; exercise training
6.  C-reactive protein genotype affects exercise training—induced changes in insulin sensitivity 
An etiologic role for chronic inflammation in the development of insulin resistance has been hypothesized. We determined whether the -732A/G and +219G/A C-reactive protein (CRP) gene variants affect insulin and glucose measures and whether these variants affect training-related changes in insulin sensitivity and glucose measures. Men and women 50 to 75 years old (n = 61) underwent baseline testing that included glucose tolerance, maximal oxygen consumption, body composition, CRP levels, and genotyping assessments. Tests were repeated after 24 weeks of aerobic exercise training. In bivariate analyses, CRP -732A/G G allele carriers had significantly lower baseline postprandial plasma glucose and after-training CRP levels. After exercise training, the -732A/G G allele carriers had ∼28% increase in insulin sensitivity index (ISI) and ∼26% reduction in insulin area under the curve (AUC), compared with the ∼7% increase in ISI and ∼15% reduction in insulin AUC in the A allele homozygotes ( P = .03). The significant enhancement of ISI in -732A/G G allele carriers remained evident in analyses limited to those with normal glucose tolerance. Multivariate analyses adjusted for demographic and biologic variables confirmed the significant enhancement of training-induced improvement in ISI by the CRP gene variant. In addition, the CRP -732A/G and +219G/A haplotype significantly associated with training-induced improvements in ISI and insulin AUC in separate multivariate models. In conclusion, the CRP -732A/G variant modulates exercise training—related improvements in ISI and glucose AUC, and the haplotype of the CRP -732A/G and +219G/A variants significantly affected training-induced changes in ISI and insulin AUC.
PMCID: PMC2643021  PMID: 16546475

Results 1-6 (6)