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.

Effect of regular exercise on homocysteine concentrations: the HERITAGE Family Study.

We investigated whether regular aerobic exercise could affect plasma total homocysteine (tHcy), and whether there were sex-related or racial differences in tHcy changes. Data were available for 816 black and white men and women, aged 17-65 years, 711 of whom completed a 20 week aerobic exercise training program. The tHcy concentration was measured in frozen plasma samples by an HPLC method. In Blacks, tHcy did not change with exercise training [men -0.5 (SD 3.7) micromol/l, women 0.0 (2.2) micromol/l) but increased significantly in Whites (men +0.3 (1.7) micromol/l, women +0.2 (1.6) micromol/l). No sex-related differences were found in either racial group. Changes in tHcy correlated negatively with baseline homocysteine (r = -0.40, P < 0.0001). Homocysteine levels of the "High" (hyperhomocysteinemia) (>or=15 micromol/l) group (n = 30) decreased significantly with regular aerobic exercise from 23.1 (12.1) to 19.6 (7.6) micromol/l. Homocysteine levels of the "Normal" group increased slightly from 8.2 +/- 2.2 to 8.5 +/- 2.4 micromol/l. Men exhibit racial differences for tHcy responses to exercise training. Regular aerobic exercise has favorable effects on individuals with hyperhomocysteinemia, but tHcy slightly increased in individuals within the normal range.

Evidence of QTLs on chromosomes 13q and 14q for triglycerides before and after 20 weeks of exercise training: the HERITAGE Family Study.

Fasting triglyceride (TG) levels in total plasma and in lipoprotein subfractions were assessed both at baseline and after a 20-week exercise training intervention in 99 White and 101 Black families. A genome-wide multipoint variance component linkage analysis was performed separately by race, using 509 markers. The strongest evidence of linkage was for the TG subfractions of low-density lipoprotein (LDL-TG) and high-density lipoprotein (HDL-TG) rather than for overall levels of TG. For baseline levels, the maximum LOD score was 3.8 on 13q12-q14 with HDL-TG in Whites. Additional linkage evidence was found on 14q31 (LOD=3.2) and 10p14 (LOD=2.9) for baseline LDL-TG in Whites. Suggestive linkage signal at baseline in Whites was detected for HDL-TG (LOD=2.6) on 12q24 and for LDL-TG on 19p13. For training response in Whites, suggestive signal (LOD=2.2) was observed on 13q12-q14 with LDL-TG and for HDL-TG on 10q23. For Blacks, weak signals (LODs<2.0) were found either for baseline and responses to training, perhaps due to small sample sizes that reduced the power of the linkage analysis. These results represent the first report of linkage for the lipoprotein subfractions and for the lipid and lipoprotein responses to exercise training. It is interesting that the strongest signals were found for the LDL-TG and HDL-TG subfractions, given their particular relationships with the atherogenic lipid profile including dense LDL and HDL particles.

Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study.

AIMS/HYPOTHESIS: Adiponectin is an adipocytokine with lowered blood levels in obesity and Type 2 diabetes mellitus. We sought to define the specific effects of different alleles of the gene encoding adiponectin. METHODS: We studied the associations of adiponectin gene sequence variations with body fat distribution and insulin indices in 503 White and 276 Black subjects of the HERITAGE Family Study cohort and subjects from a Finnish population. RESULTS: The His111 allele frequency of the Tyr111 His polymorphism in Finnish Type 2 diabetic subjects (n=254) was higher (5.1%) than in control subjects (n=270) (2.6%; P = 0.033). In the HERITAGE cohort, the His111 allele was associated with a lower insulin sensitivity index (P = 0.018) and a higher acute insulin response to glucose (P = 0.0098) in Whites. Other variants showed associations with adiposity and plasma lipid values only in Blacks. Among Blacks, the IVS2+G62T variant was associated with body fat (P = 0.002) and total cholesterol values (P = 0.005), and the Gly15Gly variant with cholesterol (P = 0.009) and triglyceride (P = 0.05) levels. The haplotype derived from these two polymorphisms was associated with total body fat, while the IVS2+G62T and Tyr111His-haplotype was associated with body fat and disposition index. CONCLUSIONS: The carriers of the His111 allele may have a higher risk of developing Type 2 diabetes mellitus. Racial differences were found between Blacks and Whites in body composition and lipids according to ACDC genotypes. Sequence variants in the adiponectin gene appear to be associated with diabetes and diabetes-related phenotypes.

Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study.

AIMS: To study the effect of exercise training on plasma C-reactive protein, a marker of inflammation. METHODS AND RESULTS: We performed a 20 week standardized exercise training programme in 652 sedentary healthy white and black men and women. C-reactive protein was measured with a high sensitivity assay. The study sample was stratified according to baseline C-reactive protein levels using a recommended classification (low <1.0 mg/L, n=265; moderate 1.0-3.0 mg/L, n=225; high >3.0 mg/L, n=162). The median C-reactive protein reduction was 1.34 mg/L in the high baseline C-reactive protein group. C-reactive protein levels did not change in the low or moderate baseline C-reactive protein groups. The difference among the C-reactive protein groups was significant adjusting for all correlates of baseline C-reactive protein (P<0.001) and additionally for changes in body weight, glucose, insulin, LDL cholesterol, HDL cholesterol, triglycerides, systolic and diastolic blood pressure, and maximal oxygen uptake (P<0.001). The C-reactive protein reduction in the high baseline C-reactive protein group was consistent across all population groups (P<0.001 for difference among baseline C-reactive protein groups). CONCLUSION: Plasma C-reactive protein levels are reduced in response to exercise training in sedentary healthy adults with high initial C-reactive protein levels. This finding may partly explain the effectiveness of regular physical activity in the prevention and treatment of cardiovascular and metabolic diseases.

Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism.

Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects. Insulin sensitivity index, glucose disappearance index, acute insulin response to glucose (AIR(glucose)), and the disposition index (DI) were obtained from the frequently sampled intravenous glucose tolerance test. White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels (p = 0.031) and sum of eight skinfolds (p = 0.003) and highest subcutaneous fat on the limbs (p = 0.002). G82A subjects had the lowest AIR(glucose) (p = 0.005) and disposition index (p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR(glucose) (p from 0.006 to 0.010). The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). In summary, PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. G82 allele heterozygotes are potentially at higher risk for type 2 diabetes. Gene-gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. The PTPN1 Pro387Leu variant was associated with lower glucose tolerance.

Common genetic and environmental effects on lipid phenotypes: the HERITAGE family study.

OBJECTIVE: Despite the well known genetic component influencing plasma lipid-lipoprotein levels and the observed correlations among these traits, little is known about pleiotropic heritable determinants among them. Our aim is to investigate pair-wise polygenic and environmental correlations among lipid-lipoprotein levels at baseline and in response to regular exercise in Whites and Blacks. METHODS: Common pair-wise genetic and environmental correlations among levels of total cholesterol (TC), LDL-C, ApoB, HDL-C (also HDL2-C and HDL3-C), triglycerides (TG, HDL-TG and LDL-TG) and ApoA-1 were investigated at baseline and again after a 20-week endurance exercise program using a variance-components-decomposition. RESULTS: With a few exceptions, all lipid phenotypes were heritable at baseline and for training responses in Blacks and Whites. Strong to high genetic and environmental correlations (0.4 < rho(g) < 0.7) were observed for the majority of the baseline pair-wise traits. For training responses, many of the same patterns were noted, although fewer genetic correlations were significant as compared to the baseline results. CONCLUSIONS: Results suggest that the observed phenotypic correlations among many of these traits may be due to in part to pleiotropic genes, in particular between LDL-C and ApoB and between TG and HDL-C. This shared genetic architecture should be considered in follow-up gene finding studies.

Effects of exercise training on glucose homeostasis: the HERITAGE Family Study.

OBJECTIVE: To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (i.v.GTT). RESEARCH DESIGN AND METHODS: An i.v.GTT was performed before and after a standardized training program in 316 women and 280 men (173 blacks and 423 whites). Participants exercised on cycle ergometers 3 days per week for 60 sessions. The exercise intensity was progressively increased from 55% VO2max for 30 min per session to 75% VO2max for 50 min per session. RESULTS: Mean insulin sensitivity increased by 10% (P < 0.001) following the intervention, but the variability in the changes was high. Men had larger improvements than women (P = 0.02). Improvements in fasting insulin were transitory, disappearing 72 h after the last bout of exercise. There were also significant mean increases in the glucose disappearance index (3%, P = 0.02) and in glucose effectiveness (11%, P < 0.001), measures of glucose tolerance and of the capacity of glucose to mediate its own disposal, respectively. The acute insulin response to glucose, a measure of insulin secretion, increased by 7% in the quartile with the lowest baseline glucose tolerance and decreased by 14% in the quartile with the highest baseline glucose tolerance (P < 0.001). The glucose area below fasting levels during the i.v.GTT was reduced by 7% (P = 0.02). CONCLUSIONS: Although the effects of structured regular exercise were highly variable, there were improvements in virtually all i.v.GTT-derived variables. In the absence of substantial weight loss, regular exercise is required for sustained improvements in glucose homeostasis.

Race and sex similarities in exercise-induced changes in blood lipids and fatness.

PURPOSE: This study explores sex and race differences in the association between changes in fat mass (FM), abdominal visceral fat (AVF), and abdominal subcutaneous fat (ASF) on blood lipid changes consequent to aerobic exercise training. METHODS: The sample included 613 participants (428 white and 185 black, 46% men) from the HERITAGE Family Study. Total FM was determined by densitometry, whereas AVF and ASF cross-sectional areas were determined by computed tomography at the L4-L5 level. Blood lipid measurements included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and the TC/HDL-C ratio, which were obtained before and after 20 wk of supervised aerobic exercise. Canonical correlation was used to determine the multivariate associations between body fatness and blood lipids at baseline and the changes induced by exercise training. RESULTS: Body fat accounted for 26-36% of the variance in baseline blood lipids, and changes in body fat accounted for 7-21% of the variance in changes in blood lipids with exercise training. The pattern of loadings indicated similar relationships between body fatness and blood lipids at baseline, and their respective changes with exercise training among the four sex-by-race groups. Greater fat loss, characterized by loss of FM, AVF, and ASF, was associated with a greater blood lipid response characterized by an increase in HDL-C and decreases in LDL-C, TG, TC, and TC/HDL-C. Although the pattern of loadings was similar in all groups, the strength of the association was stronger in blacks than in whites. CONCLUSION: The multivariate associations among fat loss and changes in blood lipids consequent to aerobic exercise training are similar in black and white men and women.

The effects of exercise training on abdominal visceral fat, body composition, and indicators of the metabolic syndrome in postmenopausal women with and without estrogen replacement therapy: the HERITAGE family study.

The purpose of this research was to investigate the effects of apriori estrogen replacement therapy (ERT) and endurance exercise training in postmenopausal women on abdominal visceral fat (AFV) and other selected variables related to body composition and the metabolic syndrome (MS). Forty-eight healthy and previously sedentary postmenopausal women (mean age, 54.3 years) who were enrolled in the HERITAGE Family Study (HFS) served as subjects. Of these 48 women, 18 were currently taking ERT and the remaining 30 were taking no supplemental estrogen (NHRT). Computed tomography (CT) scans were used to assess AVF as well as total abdominal fat (TAF) and abdominal subcutaneous fat (ASF). Body mass index (BMI) and waist-to-hip ratios (WHR) were calculated while body fat percentage (%FAT) and total fat mass (FATM) was assessed using underwater weighing. Blood assays for HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG) were conducted at a Centers for Disease Control (CDC) certified laboratory, while blood pressure measurements were assessed using an automated system. All measurements were obtained in duplicate before and after a regimen of endurance exercise training. Analysis of variance (ANOVA) showed AVF to be an average of 31.6 cm(2) less in the women receiving ERT, but lost statistical significance when AVF was adjusted for FATM. Mean values for TAF, ASF, and waist girth were also less in the women receiving ERT, but only waist girth achieved statistical significance. No differences were found in BMI or %FAT, but mean WHR was 5% smaller in the ERT group. Baseline values for HDL-C was higher and LDL-C lower in the ERT group. Prevalence of the MS tended to be greater in the NHRT group, but did not achieve statistical significance. There were no differences in training responses in any of the body composition variables between groups, however, in the ERT group LDL-C decreased with training while TG increased. It was concluded that postmenopausal women taking ERT tended to have lower values of AVF and other indicators of body composition, a more favorable lipid profile, and a slightly reduced risk of the MS when compared with women not taking supplemental hormones. Also exercise training did not improve the overall MS status of either group, as LDL-C status improved in the ERT group while TG decreased in the NHRT group.

Calcium intake is associated with adiposity in Black and White men and White women of the HERITAGE Family Study.

Calcium (Ca(2+)) intake may play a role in the regulation of body weight. Increased Ca(2+) intake has been associated with lower body weight, BMI, and adiposity measures in cross-sectional studies. We examined the association between Ca(2+) intake, derived from the Willett FFQ, and overall and abdominal adiposity in Black and White men and women of the HERITAGE Family Study. BMI, the percentage of body fat (%FAT), the sum of 8 skinfold thicknesses, computerized tomography total abdominal fat (TAF), abdominal visceral (AVF) and abdominal subcutaneous (ASF) fat, and waist circumference were measured in 362 men (109 Blacks, 253 Whites) and 462 women (201 Blacks, 261 Whites). Subjects were divided into tertiles of energy-adjusted Ca(2+) intake. Adiposity measures across tertiles were compared by ANOVA and also regressed against the energy-adjusted Ca(2+) intake to test for a linear trend. The strongest inverse associations appeared in Black men and White women. Black men in the high Ca(2+) intake group were leaner than those in the low Ca(2+) intake group: BMI 23.4 +/- 0.9 vs. 26.7 +/- 1.1 kg/m(2) (P = 0.01); for all other adiposity measures, P < 0.05. In White women, regression analyses showed significant inverse associations between Ca(2+) intake and BMI (P = 0.02), %FAT (P = 0.001), TAF (P = 0.006), AVF (P = 0.03), and ASF (P = 0.01). The percentage of fat of White men in the highest Ca(2+) intake group was significantly lower than in the lowest Ca(2+) group (P = 0.04). No significant associations were found in Black women. Low Ca(2+) intake may be associated with higher adiposity, particularly in men and White women.

Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study.

We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.

Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in Health, Risk Factors, Exercise Training, and Genetics study.

Anxiety involves complex, incompletely understood interactions of genomic, environmental, and experience-derived factors, and is currently being measured by psychological criteria. Here, we report previously nonperceived interrelationships between expression variations and nucleotide polymorphisms of the chromosome 7q21-22 acetylcholinesterase-paraoxonase 1 (ACHE-PON1) locus with the trait- and state-anxiety measures of 461 healthy subjects from the Health, Risk Factors, Exercise Training, and Genetics Family Study. The AChE protein controls the termination of the stress-enhanced acetylcholine signaling, whereas the PON protein displays peroxidase-like activity, thus protecting blood proteins from oxidative stress damages. Serum AChE and PON enzyme activities were both found to be affected by demographic parameters, and showed inverse, reciprocal associations with anxiety measures. Moreover, the transient scores of state anxiety and the susceptibility score of trait anxiety both appeared to be linked to enzyme activities. This finding supported the notion of corresponding gene expression relationships. Parallel polymorphisms in the ACHE and PON1 genes displayed apparent associations with both trait- and state-anxiety scores. Our findings indicate that a significant source of anxiety feelings involves inherited and acquired parameters of acetylcholine regulation that can be readily quantified, which can help explaining part of the human variance for state and trait anxiety.

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.

Fitness alters the associations of BMI and waist circumference with total and abdominal fat.

OBJECTIVE: We tested the following hypotheses in black and white men and women: 1) for a given BMI or waist circumference (WC), individuals with moderate cardiorespiratory fitness (CRF) have lower amounts of total fat mass and abdominal subcutaneous and visceral fat compared with individuals with low CRF; and 2) exercise training is associated with significant reductions in total adiposity and abdominal fat independent of changes in BMI or WC. RESEARCH METHODS AND PROCEDURES: The sample included 366 sedentary male (111 blacks and 255 whites) and 462 sedentary female (203 blacks and 259 whites) participants in the HERITAGE Family Study. The relationships between BMI and WC with total fat mass (determined by underwater weighing) and abdominal subcutaneous and visceral fat (determined by computed tomography) were compared in subjects with low (lower 50%) and moderate (upper 50%) CRF. The effects of a 20-week aerobic exercise training program on changes in these adiposity variables were examined in 86% of the subjects. RESULTS: Individuals with moderate CRF had lower levels of total fat mass and abdominal subcutaneous and visceral fat than individuals with low CRF for a given BMI or WC value. The 20-week aerobic exercise program was associated with significant reductions in total adiposity and abdominal fat, even after controlling for reductions in BMI and WC. With few exceptions, these observations were true for both men and women and blacks and whites. DISCUSSION: These findings suggest that a reduction in total adiposity and abdominal fat may be a means by which CRF attenuates the health risk attributable to obesity as determined by BMI and WC.

Association of apolipoprotein E polymorphism with blood lipids and maximal oxygen uptake in the sedentary state and after exercise training in the HERITAGE family study.

The relationship of apolipoprotein E (apo E) genotypes to plasma lipid and maximal oxygen uptake (Vo(2max)) was studied in the sedentary state and after a supervised exercise training program in black and white men and women. At baseline, the apo E 2/3 genotype was associated with the lowest, and apo E 3/4 and E4/4 with the highest low-density liporpotein (LDL) cholesterol and apo B levels in men and women of both races, while female (not male) carriers of apo E3 had higher high-density lipoprotein (HDL) cholesterol levels than carriers of other genotypes. Very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels were significantly higher in carriers of both apo E2 and apo E4 in white men only. Racial and sex differences were noted in lipid responses to exercise training across genotypes with a significantly greater increase in HDL cholesterol observed only in white female carriers of apo E 2/3 and E3/3, as compared to apo E4/4. Apo E polymorphism was not found to be associated with Vo(2max) levels either in the sedentary state nor the Vo(2max) response to exercise training, contrary to previous reports.

Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study.

The metabolic syndrome involves multiple and interactive effects of genes and environmental factors. To identify chromosomal regions encoding genes possibly predisposing to the metabolic syndrome, we performed a genome-wide scan with 456 white and 217 black participants from 204 nuclear families of the HERITAGE Family Study, using regression-based, single- and multipoint linkage analyses on 509 markers. A principal component analysis was performed on 7 metabolic syndrome-related phenotypes. Two principal components, PC1 and PC2 (55% of the variance), were used as metabolic syndrome phenotypes. ANOVA was used to quantify the familial aggregation of PC1 and PC2. Family membership contributed significantly (P < 0.0023) to the variance in PC1 (r(2) = 0.38 in whites; r(2) = 0.55 in blacks) and PC2 (r(2) = 0.51; r(2) = 0.48). In whites, promising evidence for linkage (P < 0.0023) was found for PC1 (2 markers on 10p11.2) and PC2 (a marker on 19q13.4). Suggestive evidence of linkage (0.01 > P > 0.0023) appeared for PC1 (1q41 and 9p13.1) and PC2 (2p22.3). In blacks, promising linkage was found for PC2 on 1p34.1, and suggestive linkage was found on 7q31.3 and 9q21.1. The genome-wide scan revealed evidence for quantitative trait loci on chromosomal regions that have been previously linked with individual cardiovascular disease and type 2 diabetes risk factors. Some of these chromosomal regions harbor promising potential candidate genes.

Apolipoprotein AI- and AI:AII-containing lipoproteins in white men and women of the HERITAGE Family study: Associations with metabolic risk profile variables.

It is now well established that an increased high-density lipoprotein (HDL) cholesterol level, especially in the HDL(2) subfraction, is associated with a reduced risk of coronary heart disease (CHD). However, little is known about the associations between the apolipoprotein (apo) composition of HDL and CHD metabolic risk factors. In the present study, we examined the gender differences in plasma concentration of HDL containing apo AI only (LpAI) versus both apoAI and apoAII (LpAI/AII), and also compared their associations with body composition, adipose tissue (AT) distribution, and metabolic risk profile variables. For that purpose, we measured fasting plasma lipoprotein-lipid levels including LpAI and LpAI/AII concentrations in a sample of 215 men and 174 women, all Caucasians, of the HERITAGE Family Study. All subjects underwent anthropometric, body fatness (underwater weighing) and abdominal AT accumulation (computed tomography) measurements. We found that, women had higher LpAI and lower LpAI/AII concentrations compared with men. Whereas in women, LpAI levels were correlated to body fat mass and waist circumference, no association between body composition, fat distribution, and LpAI concentrations was noted in men. Increased LpAI concentrations were associated with higher HDL(2) cholesterol levels in both men and women. Overall, elevated LpAI and LpAI/AII concentrations showed contrasting associations with metabolic risk profile variables as high LpAI, but not LpAI/AII concentrations were associated with a more favorable metabolic risk profile. We also found that high HDL cholesterol appeared to be more closely related to a better metabolic risk profile than high LpAI in both genders. Our results suggest that LpAI and HDL cholesterol levels are good correlates of the metabolic profile, but that HDL cholesterol concentrations could still represent a better index in CHD risk assessment.

Heart rate versus %VO2max: age, sex, race, initial fitness, and training response--HERITAGE.

PURPOSE: In the HERITAGE Family Study, heart rate (HR) associated with various percentages of maximal oxygen intake (VO2max) was used to prescribe exercise intensity. When fitness improved, HR at the same power output (PO) decreased, and PO was increased to produce the prescribed HR. Although we assumed that subjects were again working at the same %VO2max, there were no studies with a large heterogeneous population to determine whether this was correct. METHODS: Therefore, 653 subjects with complete data were classified by age, sex, race, initial VO2max, and VO2max response after 20 wk of training. RESULTS: All groups had a significant increase in VO2max and a significant decrease in HR at the same absolute PO after training but no difference in HR at the same relative intensity. CONCLUSIONS: Training does not affect HR at a given %VO2max in a heterogeneous population of men and women, blacks and whites aged 17-65 yr with different initial VO2max values and different responses to training.