Effect of exercise training on in vitro LDL oxidation and free radical-induced hemolysis: the HERITAGE Family Study.

Oxidant stress and overproduction of reactive oxygen species (ROS) contribute to the development of cardiovascular disease. Oxidative modifications of low-density lipoproteins (LDL) are thought to play an early and critical role in atherogenesis. LDL oxidation can be reproduced in vitro, but results usually show a large interindividual variation not entirely explained by the environment. Free radical-induced hemolysis is also proposed to reveal the overall antioxidant capacity. The roles of genetic factors and exercise on the variability of both measures were investigated. The study was conducted in 146 healthy individuals from 28 families participating in a 20-week exercise-training program. In addition to important biological and environmental influences on variation, significant familial aggregation was detected in all oxidation measures. Exercise did not significantly modify the LDL oxidation parameters, but significantly increased resistance was observed in the free radical-induced hemolysis, especially in women, this effect was not observed in smokers. In total, the findings suggest the presence of familial effects in the response to ex vivo oxidation. Further, smoking negates the beneficial effect of exercise training on erythrocyte resistance to free radical-induced hemolysis. These observations emphasize the importance of context in the evaluation of exercise and oxidant stress.

A genome-wide linkage scan for dietary energy and nutrient intakes: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study.

BACKGROUND: A poor diet is a risk factor for chronic diseases such as obesity, cardiovascular disease, hypertension, and some cancers. Twin and family studies suggest that genetic factors potentially influence energy and nutrient intakes. OBJECTIVE: We sought to identify genomic regions harboring genes affecting total energy, carbohydrate, protein, and fat intakes. DESIGN: We performed a genomic scan in 347 white sibling pairs and 99 black sibling pairs. Dietary energy and nutrient intakes were assessed by using Willett's food-frequency questionnaire. Single-point and multipoint Haseman-Elston regression techniques were used to test for linkage. These subjects were part of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a multicenter project undertaken by 5 laboratories. RESULTS: In the whites, the strongest evidence of linkage appeared for dietary energy and nutrient intakes on chromosomes 1p21.2 (P = 0.0002) and 20q13.13 (P = 0.00007), and that for fat intake appeared on chromosome 12q14.1 (P = 0.0013). The linkage evidence on chromosomes 1 and 20 related to total energy intake rather than to the intake of specific macronutrients. In the blacks, promising linkages for macronutrient intakes occurred on chromosomes 12q23-q24.21, 1q32.1, and 7q11.1. Several potential candidate genes are encoded in and around the linkage regions on chromosomes 1p21.2, 12q14.1, and 20q13.13. CONCLUSIONS: These are the first reported human quantitative trait loci for dietary energy and macronutrient intakes. Further study may refine these quantitative trait loci to identify potential candidate genes for energy and specific macronutrient intakes that would be amenable to more detailed molecular studies.

Familial resemblance for muscle phenotypes in the HERITAGE Family Study.

INTRODUCTION/PURPOSE: We hypothesized that skeletal muscle histological and biochemical phenotypes aggregate within families. METHODS: Nineteen families (78 Caucasians) from the HERITAGE Family Study participated in the study. Proportions and areas of Type I, IIA, and IIX muscle fibers, capillary density, and maximal enzyme activities were determined in biopsy samples from the vastus lateralis obtained in the sedentary state and after a 20-wk endurance-training program. RESULTS: In the sedentary state, there was evidence for familial resemblance for Type I fiber area (P = 0.007), number of capillaries around Type I and Type IIA fibers (P = 0.04), and Type I and IIA fiber areas per capillary (P = 0.01 and P = 0.04, respectively). Significant familial aggregation (0.05>P > 0.0001) was observed for maximal activities of enzymes of the energy production pathways. With regard to the training response, significant familial aggregation (0.05 > P < 0.0001) was observed for maximal activities of enzymes of the energy production pathways. CONCLUSION: These data provide evidence of familial aggregation for enzyme activities of the main energy metabolism pathways of the skeletal muscle in the sedentary state and in response to regular exercise.

Role of ghrelin polymorphisms in obesity based on three different studies.

OBJECTIVE: Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. RESEARCH METHODS AND PROCEDURES: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. RESULTS: Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin-like growth factor-1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p < 0.05) in SOS subjects whose BMI was < or =25 kg/m(2) than in those with BMI >25 kg/m(2) (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%). DISCUSSION: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.

A genome-wide linkage scan for steroids and SHBG levels in black and white families: the HERITAGE Family Study.

To identify loci-harboring genes affecting steroid hormone and SHBG plasma levels, a genomic-wide scan was performed in the HERITAGE Family Study at baseline. The following steroid hormones were assayed: androstane-3 alpha, 17 beta-diol glucuronide, androsterone glucuronide, cortisol, dihydrotestosterone, estradiol, 17-hydroxyprogesterone (OH-PROG), progesterone (PROG), pregnenolone ester, and testosterone. A total of 509 markers on the 22 autosomes were genotyped, and a maximum of 357 pairs of siblings from white families and 103 from black families were available for the study. Significant linkages with LOD scores over 3.6 (P < 2.2 x 10(-5)) for SHBG were observed in blacks on 1q44 (D1S321), 5p13.3 (D5S1986), 10q24.1 (D10S1239), and 12q12 (D12S1653) in both singlepoint and multipoint analyses. Promising evidence of linkage (1.75 < LOD < 3.6; 2.2 x 10(-5) < P < 0.0023) for SHBG was observed on 1q44 in singlepoint analysis in whites. In addition, several other loci in blacks exhibited promising evidence of linkage, suggesting that many genes can potentially regulate SHBG levels. In the case of C21 steroids, promising linkages were found on 1q43 (D1S517) for PROG, 2p25.1 (D2S1400) for pregnenolone ester, and 18q21.32 (D18S38) for OH-PROG in whites and on 3q25.33 (D3S1763) for OH-PROG in blacks, both singlepoint and multipoint analyses (P < 0.0023). The strongest signals for C19 steroids were found on 22q12.3 for testosterone in whites (P = 0.0024 in multipoint) and on 8q22.1 for dihydrotestosterone in blacks. In blacks, the strongest evidence of linkage for estradiol (C18 steroid) was provided by marker D1S1588 on 1p21.3 and in whites by markers D2S2374 and D2S2347 on 2p21, and D6S465 on 6p12.3. Several genes encoding enzymes of the steroid biosynthesis pathways but also other potential candidate genes were located in the vicinity of the genomic regions showing evidence of linkage in this genomic scan.

Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study.

PURPOSE: To investigate the influences of menopause, hormone replacement, and endurance exercise training on cardiovascular hemodynamics and oxygen uptake parameters during exercise in women. METHODS: Subjects were 338 premenopausal women, 29 postmenopausal women taking hormone replacement, and 28 postmenopausal women not taking hormone replacement, all enrolled in the HERITAGE Family Study. Hemodynamic and oxygen uptake data were gathered on a cycle ergometer at 50 watts (W), 60% peak oxygen uptake, and at peak exercise, both before and after a 20-wk regimen of endurance exercise training on a cycle ergometer. RESULTS: Systolic blood pressure (SBP) during peak exercise was found to be an average of 14 mm Hg less in postmenopausal women receiving hormones than in those not receiving hormones. Furthermore, menopause was associated with a 26.2 mm Hg higher SBP at 50 W power output, which remained physiologically significant after adjustment for age. At 50 W, postmenopausal women not taking hormones showed a 13.8 mm Hg greater training-induced reduction in SBP than those taking hormones. CONCLUSION: It was concluded that hormone replacement may be associated with a vasodilatory reserve at high exercise intensities and that endurance exercise training elicits favorable hemodynamic and oxygen uptake adaptations during exercise that are, in most instances, independent of menstrual status or hormone replacement.