Hepatic lipase gene -514C>T variant is associated with exercise training-induced changes in VLDL and HDL by lipoprotein lipase.

Our objective was to test the hypothesis that a common polymorphism in the hepatic lipase (HL) gene (LIPC -514C>T, rs1800588) influences aerobic exercise training-induced changes in TG, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) through genotype-specific increases in lipoprotein lipase (LPL) activity and that sex may affect these responses. Seventy-six sedentary overweight to obese men and women aged 50-75 yr at risk for coronary heart disease (CHD) underwent a 24-wk prospective study of the LIPC -514 genotype-specific effects of exercise training on lipoproteins measured enzymatically and by nuclear magnetic resonance, postheparin LPL and HL activities, body composition by dual energy x-ray absorptiometry and computer tomography scan, and aerobic capacity. CT genotype subjects had higher baseline total cholesterol, HDL-C, HDL(2)-C, large HDL, HDL particle size, and large LDL than CC homozygotes. Exercise training elicited genotype-specific decreases in VLDL-TG (-22 vs. +7%; P < 0.05; CC vs. CT, respectively), total VLDL and medium VLDL, and increases in HDL-C (7 vs. 4%; P < 0.03) and HDL(3)-C with significant genotype×sex interactions for the changes in HDL-C and HDL(3)-C (P values = 0.01-0.02). There were also genotype-specific changes in LPL (+23 vs. -6%; P < 0.05) and HL (+7 vs. -24%; P < 0.01) activities, with LPL increasing only in CC subjects (P < 0.006) and HL decreasing only in CT subjects (P < 0.007). Reductions in TG, VLDL-TG, large VLDL, and medium VLDL and increases in HDL(3)-C and small HDL particles correlated significantly with changes in LPL, but not HL, activity only in CC subjects. This suggests that the LIPC -514C>T variant significantly affects training-induced anti-atherogenic changes in VLDL-TG, VLDL particles, and HDL through an association with increased LPL activity in CC subjects, which could guide therapeutic strategies to reduce CHD risk.

APOE genotype affects black-white responses of high-density lipoprotein cholesterol subspecies to aerobic exercise training.

The objective of the study was to determine whether ethnicity interacts with the APOE genotype to influence conventionally measured high-density lipoprotein cholesterol (HDL-C) subfraction levels and nuclear magnetic resonance-measured (HDL(NMR)-C) particle size at baseline and after training, and the changes with training. After a 6-week dietary stabilization period, men and postmenopausal women 50 to 75 years old underwent baseline testing (NMR lipid, maximum oxygen consumption, body composition, and genotyping assessments). Tests were repeated after completing 24 weeks of endurance exercise training. At baseline, APOE2/3 blacks had significantly larger particle size (P < .001) and higher total HDL(NMR)-C particle concentration (P = .006) than whites. After 6 months of endurance exercise training, APOE2/3 blacks maintained a significantly larger HDL(NMR)-C particle size (P < .001) and particle concentration of the large HDL(NMR)-C than APOE2/3 whites (P < .001). In multivariate analyses of variance adjusted for demographic and environmental confounding factors and for training-induced changes in lean body mass and intraabdominal fat, the model explained approximately 33% of the observed variability in training-induced improvements in HDL(NMR)-C particle size (P = .002), with APOE2/3 blacks having a greater increase in training-induced changes in HDL(NMR)-C particle size. In a separate but similarly adjusted model for conventionally measured HDL(2)-C, the model explained approximately 49% of the observed variability in training-induced changes in HDL(2)-C. Ethnicity interacted with the E2/3 genotype at the APOE gene locus to influence higher baseline and after-training levels, and greater exercise training-induced improvements in the advantageous HDL-C subfractions in blacks than in whites. APOE2/3 blacks may benefit more from aerobic fitness to reduce cardiovascular risk.

Oxidative stress levels are reduced in postmenopausal women with exercise training regardless of hormone replacement therapy status.

This study investigated whether postmenopausal women on HRT would experience a greater reduction in oxidative stress after 24 weeks of aerobic exercise training compared to postmenopausal women not on HRT. Plasma thiobarbituric acid reactive substances (TBARS), an indicator of oxidative stress, was measured in 48 previously sedentary postmenopausal women on HRT (n = 21) and not on HRT (n = 27) before and after 24 weeks of aerobic exercise training. Baseline levels of TBARS differed significantly between groups after controlling for age, BMI, and fasting blood glucose (P = 0.03). There was a significant reduction in TBARS after 24 weeks of training in the overall group. When analyzed separately, both postmenopausal women on HRT and those not on HRT had a significant reduction in TBARS; however, there was no significant difference between groups (-0.71 +/- 0.14 nmol/ml in non-HRT users vs. -0.50 +/- 0.16 nmol/ml in HRT users; P = 0.33) even after controlling for age, BMI, and baseline levels of TBARS. Our results showed that aerobic exercise training significantly decreased oxidative stress in postmenopausal women; however, both HRT users and non-HRT users benefited equally.

Variation in the human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) gene is associated with plasma soluble LOX-1 levels.

The lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) expressed on vascular cells plays a major role in atherogenesis by internalizing and degrading oxidized low-density lipoprotein. 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 gene 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 with both the CT (P=0.02) and TT genotype groups (P=0.002). Plasma sLOX-1 levels were also significantly higher in the 501GC genotype group compared with the GG genotype group (P=0.004). In univariate analyses, sLOX-1 levels were significantly associated with both the 3'UTR-C/T and G501C polymorphisms. These associations remained significant after adjusting for age, sex, race and body mass index. In conclusion, variation in the LOX-1 gene is associated with plasma sLOX-1 levels in older men and women.

Elevated soluble lectin-like oxidized LDL receptor-1 (sLOX-1) levels in obese postmenopausal women.

We investigated the association between soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels and obesity in older women. Fifty-one postmenopausal women (10 lean, 22 overweight, and 19 obese) were included in this small retrospective analysis. Plasma sLOX-1 levels were measured using a chemiluminescent enzyme-linked immunoassay. 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, hormone replacement therapy, and body fat. In conclusion, obese women have higher sLOX-1 levels, which may reflect increased LOX-1 expression in adipose tissue.

Association between KCNJ11 E23K genotype and cardiovascular and glucose metabolism phenotypes in older men and women.

Our objective was to investigate the relationship between the E23K genetic variant in the KCNJ11 gene, which encodes for the Kir6.2 subunit of the inward rectifier K+ channel family, and glucose and insulin metabolism and cardiovascular (CV) function in the sedentary state and their responses to exercise training. Two hundred and fourteen healthy sedentary men and women aged 50-75 years old and free of CV disease and type 2 diabetes underwent baseline testing (maximal oxygen consumption (Vo2max), body composition and glucose tolerance). One hundred and sixty-three of them repeated these tests after 24 weeks of exercise training while on a low-fat diet. At baseline, age, height, body fat, resting systolic blood pressure and all glucose and insulin metabolism markers did not differ among E23K genotype groups. In women at baseline, E23K genotype was associated with body weight, body mass index, Vo2max (ml kg(-1) min(-1), l min(-1)) and maximal minute ventilation. In men at baseline, E23K genotype was significantly associated with maximal heart rate, maximal respiratory exchange ratio and diastolic blood pressure at rest. Numerous glucose and insulin metabolism and CV function phenotypes changed significantly with exercise training in the total population. The E23K genotype did not significantly influence any of these training-induced changes. Thus, the common E23K genetic variant at the KCNJ11 gene locus was significantly associated with CV function in the untrained state, although the associations appear to differ between men and women. However, this variant has no significant effect on training-induced CV and glucose and insulin metabolism adaptations.

Differential aerobic exercise-induced changes in plasma aldosterone between African Americans and Caucasians.

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.

Exercise training-induced changes in coagulation factors in older adults.

UNLABELLED: The coagulation cascade plays a critical role in the development of cardiovascular disease (CVD). Elevated plasma prothrombin fragment 1 + 2 (F1 + 2) and factor VIII antigen (FVIII:Ag) levels have been associated with a hypercoagulable state, enhancing the risk for vascular thrombotic events. Aerobic training is known to reduce CVD risk, and an improved coagulation profile may contribute to this reduction. PURPOSE: To analyze the effect of 6 months of standardized aerobic exercise training on resting F1 + 2 and FVIII:Ag levels in men and postmenopausal women aged 50-75 while accounting for several possibly confounding factors. MATERIALS AND METHODS: Sedentary men (N=16) and women (N=31) underwent supervised aerobic training 3 d x wk(-1) for 6 months while maintaining the American Heart Association step 1 diet. Baseline and final testing included measurement of F1 + 2, FVIII:Ag, plasma lipoprotein-lipid levels, body composition, and VO2max. RESULTS: When adjusted for baseline values and changes in diastolic blood pressure with training, F1 + 2 was found to decrease significantly with exercise training from 1.493 +/- 0.058 to 1.422 +/- 0.059 nM (P=0.014). FVIII:Ag levels were found to increase significantly with training when adjusted for baseline values, from 152.5 +/- 6.7% of standard at baseline to 156.0 +/- 6.1% of standard at final testing (P=0.005). Training-induced changes in coagulation markers were independent of changes in blood lipids, aerobic capacity, and body composition. CONCLUSIONS: : These results indicate that endurance training has a significant impact on the coagulation cascade, reducing coagulation activity in the common pathway and thrombin formation at rest while increasing the activation potential of the intrinsic pathway.

Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women.

Endurance exercise training improves plasma lipoprotein and lipid profiles and reduces cardiovascular disease risk. However, the effect of endurance exercise training, independent of diet and body fat phenotypes, on plasma lipoprotein subfraction particle concentration, size, and composition as measured by nuclear magnetic resonance (NMR) spectroscopy is not known. We hypothesized that 24 weeks of endurance exercise training would independently improve plasma lipoprotein and lipid profiles as assessed by both conventional and novel NMR measurement techniques. One hundred sedentary, healthy 50- to 75-year-olds following a standardized diet were studied before and after 24 weeks of aerobic exercise training. Lipoprotein and lipid analyses, using both conventional and NMR measures, were performed at baseline and after 24 weeks of exercise training. Relative and absolute maximum oxygen consumption increased 15% with exercise training. Most lipoprotein and lipid measures improved with 24 weeks of endurance exercise training, and these changes were consistently independent of baseline body fat and body fat changes with training. For example, with exercise training, total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) decreased significantly (2.1+/-1.8 mg/dL, P=.001; -17+/-3.5 mg/dL, P<.0001; and -0.7+/-1.7 mg/dL, P<.0001, respectively), and high-density lipoprotein cholesterol subfractions (HDL3-C and HDL2-C) increased significantly (1.9+/-0.5 mg/dL, P=.01, and 1.2+/-0.3 mg/dL, P=.02, respectively). Particle concentrations decreased significantly for large and small very low-density lipoprotein particles (-0.7+/-0.4 nmol/L, P<.0001, and -1.1+/-1.7 nmol/L, P<.0001, respectively), total, medium, and very small LDL particles (-100+/-26 nmol/L, P=.01; -26+/-7.0 nmol/L, P=.004; and -103+/-27 nmol/L, P=.02, respectively), and small HDL particles (-0.03+/-0.4 micromol/L, P=.007). Mean very low-density lipoprotein particle size also decreased significantly (-1.7+/-0.9 nm, P<.0001) and mean HDL particle size increased significantly with exercise training (0.1+/-0.0 nm, P=.04). These results show that 24 weeks of endurance exercise training induced favorable changes in plasma lipoprotein and lipid profiles independent of diet and baseline or change in body fat.

FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women.

BACKGROUND: A common functional missense mutation [Ala54Thr of the fatty acid-binding protein 2 gene (FABP2)] has previously been studied for associations with glucoregulation, postprandial lipemia, and lipid oxidation rates. However, most of those studies have not accounted for the interactive and potentially confounding effects of habitual physical activity and diet. OBJECTIVE: We tested the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet, Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous counterparts. DESIGN: Men and women (n = 122) aged 50-75 y who were following a low-fat diet were genotyped and underwent oral-glucose-tolerance tests. A subgroup (n = 36) also underwent postprandial lipemia tests with lipid oxidation rate measurements. RESULTS: Thr54 carriers were less likely to have normal glucose tolerance (P = 0.05) and had higher fasting glucose concentrations (P = 0.003) than did Ala54 homozygotes. In Thr54 carriers, the insulin sensitivity index was lower (P = 0.02), and the fasting insulin and the oral-glucose-tolerance test insulin area under the curve were higher (P = 0.05 and 0.03, respectively) than in Ala54 homozygotes. FABP2 genotype was not associated with fasting or postprandial lipemia test triacylglycerol or free fatty acids (P > or = 0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01), which suggests that fat absorption is higher in Thr54 carriers than in Ala54 homozygotes. CONCLUSIONS: In sedentary nondiabetic persons following a low-fat diet, FABP2 Thr54 carriers have lower glucose tolerance and lower insulin action than do Ala54-homozygous persons. Furthermore, FABP Thr54 carriers have higher lipid oxidation rates, which may be the mechanism of glucoregulatory dysfunction.

Role of potassium excretion and percent body fat on ethnic differences in plasma aldosterone levels.

OBJECTIVE: To determine whether plasma aldosterone (PA) levels differed between African American and White prehypertensives and if so, could the difference be explained by ethnicity-related variability in urinary K+ and Na+ excretion, body mass index (BMI), and percent body fat. DESIGN: Ethnic comparison SETTING: The University of Maryland College Park and the University of Maryland School of Pharmacy. PARTICIPANTS: 61 (African American, n=28; White, n=33) prehypertensives (systolic blood pressure [SBP] 131 +/- 10 mm Hg, diastolic blood [DBP] 85 +/- 6 mm Hg). INTERVENTION: 6-week dietary stabilization and medication tapering period. MAIN OUTCOME MEASURES: PA levels, Na+ and K+ excretion, blood pressure, and percent body fat and BMI. RESULTS: We saw no differences in SBP (P=.36) and DBP (P=.54) between the two ethnic groups. PA levels were lower in African Americans compared to Whites (62 +/- 7 vs 107 +/- 12 pg/mL, P=.002). 24-hour K+ excretion was lower among African Americans compared to Whites (51 +/- 7 vs 70 +/- 4 mmol/day, P=.002). We saw no difference in percent body fat, BMI, SBP, or DBP between African Americans and Whites. After separately accounting for K+ excretion and Na+ excretion and BMI, plasma aldosterone levels remained significantly different between the two ethnic groups. After adjusting for percent body fat, PA levels were not significantly different between the two ethnic groups (P = .06). CONCLUSIONS: The findings of the current study indicate that PA levels differ between African American and White prehypertensives and this difference may partly be due to ethnic variability in K+ excretion and percent body fat.

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 approximately 28% increase in insulin sensitivity index (ISI) and approximately 26% reduction in insulin area under the curve (AUC), compared with the approximately 7% increase in ISI and approximately 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.

Human gender differences in fibrinolytic responses to exercise training and their determinants.

Endurance exercise training improves fibrinolysis, but this training-induced adaptation may differ somewhat between men and women. We sought to determine whether the potential gender differences in training-induced changes in selected fibrinolysis measures were related to changes in adiposity and/or plasma lipoprotein lipid levels. Seventeen men and 28 women, 50-75 years old, who were generally overweight to obese, were assessed for plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) activity, t-PA antigen and plasma lipoprotein-lipid levels, and body composition before and after 6 months of endurance exercise training while on a low-fat diet. At baseline, there were no differences in fibrinolytic measures between the men and women. Baseline levels of these fibrinolytic markers in both men and women were primarily related to other fibrinolytic measures and body composition, with a smaller contribution from plasma high-density lipoprotein cholesterol (HDL-C) levels. Exercise training reduced t-PA antigen levels in both men and women, but the reduction was significantly greater in men (-1.6 +/- 0.3 versus -0.5 +/- 0.2 ng ml(-1), P = 0.007). Exercise training decreased PAI-1 activity more in men than in women (-2.6 +/- 1.4 versus +0.9 +/- 0.9 IU ml(-1), P = 0.03). Men and women both showed increased t-PA activity with exercise training to the same extent (+0.38 +/- 0.12 versus +0.36 +/- 0.24 U ml(-1)). The changes in fibrinolytic measures with exercise training in men and women were correlated with changes in other fibrinolytic measures, although in men abdominal fat changes were a strong predictor of fibrinolytic changes with training. These findings suggest that training-induced improvements in endogenous fibrinolysis markers are somewhat greater in men compared to women and may be more strongly associated with abdominal obesity in men.

NADPH oxidase p22phox gene variants are associated with systemic oxidative stress biomarker responses to exercise training.

Systemic oxidative stress plays a role in many degenerative diseases. Although regular physical activity has been known as the most effective nonpharmacological intervention to alleviate the oxidative stress, the beneficial effect varies between individuals. We investigated whether NADPH oxidase p22phox gene C242T and A640G polymorphisms are associated with systemic oxidative stress level response to exercise training (ExTr). Fifty-nine sedentary middle-aged to older Caucasians with relatively high cardiovascular disease risk factors underwent a 6-mo standardized ExTr program. Body mass index, plasma lipoprotein-lipid profiles, cardiovascular fitness, and plasma thiobarbituric acid reactive substances (TBARS) were measured before and after ExTr. Demographic and initial levels of cardiovascular disease risk factors were similar among genotype groups for both polymorphisms. Overall, TBARS was decreased by 16% with ExTr in the entire group (P < 0.001). There was no significant difference in TBARS changes with ExTr among the C242T genotype groups. However, A allele carriers showed greater reduction in TBARS than noncarriers at the A640G locus (P = 0.05). There was a significant interaction (P = 0.05) between ExTr and A640G polymorphism in TBARS changes with ExTr. This interaction remained after accounting for age and baseline TBARS level. Furthermore, diplotype analysis showed that TBARS was decreased to a greater extent in the C242/A640 haplotype carriers compared with the noncarriers (P < 0.05). We found that p22phox polymorphisms, especially A640G, were associated with differential changes in systemic oxidative stress with aerobic exercise training.

Interleukin-6 genotype is associated with high-density lipoprotein cholesterol responses to exercise training.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and its subfractions are modifiable with exercise training and these responses are heritable. The interleukin-6 (IL6)-174G/C polymorphism may be associated with HDL-C levels. We hypothesized that the IL6-174G/C polymorphism would be associated with plasma HDL-C response to exercise training. METHODS AND RESULTS: Sixty-five 50- to 75-year-olds on a standardized diet were studied before and after 24 weeks of aerobic exercise training. Significant differences existed among genotype groups for change with exercise training in HDL-C, HDL3-C, integrated HDL4,5NMR-C, and HDLsize. The CC genotype group increased HDL-C more than the GG (7.0 +/- 1.3 v. 1.0 +/- 1.1 mg/dL, p = 0.001) and GC groups (3.3 +/- 0.9 mg/dL, p = 0.02); for HDL3-C, the CC group increased more than the GG (6.1 +/- 1.0 v. 0.9 +/- 0.9, mg/dL p < 0.001) and GC groups (2.5 +/- 0.7 mg/dL, p = 0.006). Integrated HDL4,5NMR-C increased more in the CC than GG group (6.5 +/- 1.6 mg/dL v. 1.0 +/- 1.3 mg/dL, p = 0.01), as did HDLsize compared to the GG (CC: 0.3 +/- 0.1 v. GG: 0.1 +/- 0.1 nm, p = 0.02) and GC (0.0 +/- 0.0 nm, p = 0.007) groups. CONCLUSIONS: IL6 genotype is associated with HDL-C response to exercise training.

Vitamin D receptor FokI genotype influences bone mineral density response to strength training, but not aerobic training.

To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50-81 years old) were studied before and after approximately 5-6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD (P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD (P = 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT.

Endurance training-induced changes in the insulin response to oral glucose are associated with the peroxisome proliferator-activated receptor-gamma2 Pro12Ala genotype in men but not in women.

The present study sought to investigate, in sedentary men and women, (a) whether a common functional gene variant (peroxisome proliferator-activated receptor-gamma2 [PPARgamma2] Pro12Ala) predicts insulin action and (b) whether improvements in insulin action in response to endurance exercise training are associated with PPARgamma2 Pro12Ala. Sedentary, 50- to 75-year-old men and women (N = 73) were genotyped and underwent oral glucose tolerance tests (OGTTs) before and after 6 months of endurance training. At baseline, men heterozygous for the Pro12Ala variant had a greater OGTT insulin area under the curve (AUC) as compared with Pro12 homozygous men (P = .009). Endurance training resulted in a significantly greater improvement in insulin AUC in Pro12Ala heterozygous men as compared with Pro12 homozygous men (P = .003) despite no genotype-specific differences with respect to training-induced changes in body weight, body mass index, and percent body fat. No differences between genotype groups were present at baseline or in response to training in women. Training did not alter the OGTT glucose AUC for the group as a whole, and the baseline, final, and change in glucose AUC were not dependent on PPARgamma2 genotype and/or sex. In conclusion, these findings suggest that sedentary men with the PPARgamma2 Pro12Ala variant have lower insulin action on glucose disposal as compared with their counterparts. However, these men are particularly responsive with respect to the magnitude of endurance training-induced improvement in insulin action.

C-reactive protein genotypes affect baseline, but not exercise training-induced changes, in C-reactive protein levels.

OBJECTIVE: 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. CONCLUSIONS: 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.

Influence of the interleukin-6 -174 G/C gene polymorphism on exercise training-induced changes in glucose tolerance indexes.

A polymorphism in the IL-6 gene, a G-to-C substitution 176 bp upstream of the ATG translation initiation site, has been associated with diabetes prevalence and insulin resistance. Interventions including exercise training are frequently used to modify cardiovascular disease risk factors. Consequently, this project examined associations between the IL-6 -174 genotype and oral glucose tolerance test outcomes in 50- to 75-yr-old sedentary men and postmenopausal women before and after aerobic exercise training. Among the 87 individuals who started the study, 56 were retested after 6 mo of aerobic exercise training. Subject characteristics at baseline did not differ between the IL-6 genotype groups with the exception of fasting glucose, which was higher (P = 0.02, covariates age, gender, and ethnicity) in the CC genotype group. The training-induced change in glucose area under the curve during the oral glucose tolerance test varied between the IL-6 -174 genotype groups (P = 0.05, covariates age, gender, ethnicity, baseline glucose area under the curve, and percent body fat change) with a significant decrease occurring only in the GG genotype group. Insulin outcomes did not differ among the groups at baseline or after training. Training-induced changes in weight, percent body fat, maximal oxygen consumption, fasting glucose, and an insulin sensitivity index also changed similarly among the genotype groups. In conclusion, fasting glucose and the extent to which glucose tolerance changes with exercise training may be influenced by the IL-6 -174 gene polymorphism.

Plasma nitrate/nitrite response to an oral glucose load and the effect of endurance training.

To assess the role of circulating nitric oxide (NO) production in glucose homeostasis, plasma nitrate/nitrite (NO(x)) was assessed during oral glucose tolerance tests (OGTTs) on 64 sedentary subjects and in a subset 40 subjects before and after 6 months of endurance exercise training. NO(x) decreased with the oral glucose load (P