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Biomedical subjects

J H Wilmore

Publications and source records attributed to J H Wilmore.

At least 19 recordsLinked to original sources

Associations between cardiorespiratory responses to exercise and the C34T AMPD1 gene polymorphism in the HERITAGE Family Study.

The associations of the C34T polymorphism of the adenosine monophosphate deaminase 1 (AMPD1) gene with cardiorespiratory phenotypes were tested during cycling exercise at absolute and relative power outputs progressing to exhaustion before and after endurance training for 20 wk in the HERITAGE Family Study cohort (n = 779). Since no blacks were mutant homozygotes (TT), only whites were considered for analysis (400 normal homozygotes, CC; 97 heterozygotes, CT; and 6 TT). For sedentary state, cycling at the absolute power output of 50 W resulted in a higher rating of perceived exertion in TT (P < 0.0001). At the relative intensity of 60% of Vo(2 max), stroke volume was lower in TT (P < 0.05). Maximal values for power output, systolic blood pressure, heart rate, Vco(2), and respiratory exchange ratio were lower in TT (P < 0.05). The cardiorespiratory training response at 50 W and at 60% of Vo(2 max) was similar across C34T-AMPD1 genotypes. However, the maximal values for ventilation, Vo(2), and Vco(2) during exercise increased less in TT (P < 0.01). The results indicate that subjects with the TT genotype at the C34T AMPD1 gene have diminished exercise capacity and cardiorespiratory responses to exercise in the sedentary state. Furthermore, the training response of ventilatory phenotypes during maximal exercise is more limited in TT.

AMP Deaminase↗

Interactions among the beta2- and beta3- adrenergic receptor genes and total body fat and abdominal fat level in the HERITAGE Family Study.

OBJECTIVE AND SUBJECTS: Interactions between markers in the beta2- and beta3-adrenergic receptor (ADR) genes and total body fat and computerized tomography-measured abdominal fat phenotypes were studied in the HERITAGE Family Study cohort of Black (n=205; 81 males and 124 females) and White (n=415; 198 males and 217 females) subjects before and after an endurance training program. RESULTS: In Black subjects, beta2- and beta3-ADR gene variants showed evidence of interactions on changes in total body fat mass and abdominal fat area (P<0.005 and =0.010, respectively). Black subjects who were carriers of both beta2-ADR Arg16 and beta3-ADR Arg64 alleles had a greater decrease in total fat mass as well as abdominal total and subcutaneous, but not visceral fat areas in response to endurance training than subjects with other genotype combinations (P from 0.011 to 0.047). After correction for multiple tests, the findings remained essentially unchanged for total body fat mass and abdominal fat area, but became nonsignificant for subcutaneous fat area. The changes in abdominal fat correlated positively with the changes in fat mass (P<0.0001). The interactions between beta2 and beta3-ADR gene markers accounted for a maximum of 3% of the variances in the response of total fat mass and abdominal fat area to endurance training in Black subjects but it was not significant in White subjects. CONCLUSION: Interactions between sequence variants in the beta2-beta3-ADR gene contributed to the changes in fat mass and abdominal adiposity in response to endurance training in Black subjects.

Abdomen↗

The agouti-related protein and body fatness in humans.

OBJECTIVE: The objective of this study was to examine the impact of a single nucleotide polymorphism (SNP) (-38C>T) in the promoter of the human agouti-related protein (hAgRP) gene on promoter affinity for transcription factors (TFs) and its possible association with body composition phenotypes. DESIGN: Electrophoretic mobility shift assays for the functional studies and association analyses for the population studies. SUBJECTS AND METHODS: Nuclear extracts were isolated from the mouse hypothalamus cell line GT1-7 and subjected to binding assays using oligonucleotide probes corresponding to the -38C>T region and an antibody for the E12/E47 TFs. Individuals (n = 259) from the HERITAGE Family Study were genotyped for the -38C>T SNP and used in the association studies. RESULTS: Electrophoretic mobility shift and supershift assays confirmed binding of the E12/E47 TF to the -38C>T site in a genotype-dependent manner. The T allele was found exclusively in the black subjects while the genotype with the higher binding affinity, CC, was significantly associated with high BMI, fat mass, and percent body fat in the black subjects of the HERITAGE Family Study. CONCLUSIONS: The E12/E47 TF could play a role in the regulation of hAgRP expression while the population studies suggest that the TT genotype of the -38C>T SNP could play a protective role against the development of obesity in the black population of the HERITAGE Family Study.

Adipose Tissue↗

Familial aggregation of exercise heart rate and blood pressure in response to 20 weeks of endurance training: the HERITAGE family study.

Changes of heart rate (HR) and blood pressure (BP) relative to baseline levels in response to an extended period of endurance training are indices of cardiovascular adaptability. Familial influences were investigated for HR and BP at work rates of 50 W and 60 % of the maximal oxygen uptake (VO2max) in response to 20 weeks of endurance training. A total of 481 participants from 99 sedentary White nuclear families in the HERITAGE Family Study (HERITAGE) were analyzed using a familial correlation model. Each of these training response phenotypes was adjusted for the effects of age, BMI, cigarette smoking, baseline VO2max, and its baseline values in fathers, mothers, sons and daughters, respectively. We found that maximal heritabilities reached 34 % and 29 % for HR training responses at 50 W and 60 % of VO2 max, respectively. The heritability was 22 % for systolic BP (SBP) training response at 50 W, but negligible at 60 % of VO2max. No significant heritabilities were found for diastolic BP (DBP) training responses at either 50 W or 60 % of VO2max. Familial influences for exercise HR and BP training responses were also assessed in a total of 257 participants from 113 Black family units in HERITAGE. However, there was no significant familial resemblance, which may be attributable to the small sample size. In conclusion, HR and SBP training responses during submaximal exercise in Whites were influenced by a modest, but significant, familial component. These observations are therefore in contrast to substantial familial effects (heritability estimates of about 50 %) previously reported for these variables measured at baseline.

Adaptation, Physiological↗

Evidence of major genes for exercise heart rate and blood pressure at baseline and in response to 20 weeks of endurance training: the HERITAGE family study.

Major gene effects on exercise heart rate (HR) and blood pressure (BP) measured at 50 W and 80 % maximal oxygen uptake (VO (2)max) were assessed in 99 White families in the HERITAGE Family Study. Exercise HR and BP were measured both before and after 20 weeks of endurance training. The baseline phenotypes were adjusted for the effects of age and BMI, whereas the training responses (post-training minus baseline) were adjusted for the effects of age, BMI and the corresponding baseline values, within four sex-by-generation groups. Baseline exercise HR at 50 W was under the influence of a major recessive gene and a multifactorial component, which accounted for 30 % and 27 % of the variance, respectively. The training response was found to be under the influence of a major dominant gene, which accounted for 27 % of the variance. These significant major gene effects were independent of the effects of cigarette smoking, baseline VO (2)max, and the resting HR levels. No significant interactions were found between genotype and age, sex, or BMI. No major gene effect was found for exercise BP. Instead, we found the baseline exercise BP at 50 W and 80 % VO (2)max and the training response at 50 W were solely influenced by multifactorial effects, which accounted for about 50 %, 40 % and 20 % of the variance, respectively. No familial resemblance was found for training responses in exercise HR or BP at 80 % VO (2)max. Segregation analysis also was carried out for exercise HR in Whites pooled with a small sample of Blacks in HERITAGE. Similar major effects were found, but the transmission from parents to offspring did not follow Mendelian expectations, suggesting sample heterogeneity. In conclusion, submaximal exercise HR at baseline and in response to endurance training was influenced by putative major genes, with no evidence of interactions with sex, age or BMI, in contrast to a multifactorial etiology for exercise BP.

Black People↗

The hormone-sensitive lipase gene and body composition: the HERITAGE Family Study.

OBJECTIVE: To investigate whether the C-60G polymorphism and other markers in the hormone-sensitive lipase (LIPE) gene are associated with baseline body composition and free-fatty acid (FFA) concentrations measured at rest and during low-intensity exercise in white and black subjects participating in the HERITAGE Family Study. SUBJECTS: Adult sedentary white (245 men and 258 women) and black (91 men and 185 women) subjects. MEASUREMENTS: body mass index (BMI); fat mass (FAT); percentage body fat (%FAT); fat-free mass (FATFR); sum of eight skinfolds (SF8); subcutaneous (ASF), visceral (AVF) and total (ATF) abdominal fat areas assessed by CT scan; plasma FFA concentrations measured at rest (FFAR), at a power output of 50 W (FFA50) and at a relative power output of 60% of VO(2max) (FFA60%); and fasting insulin (INS). STATISTICAL ANALYSIS: Association between the C-60G polymorphism of the LIPE gene and each phenotype was tested separately in men and women using ANCOVA with the effects of age and race as covariates and with further adjustment for FAT for ASF, AVF, ATF, FFAR, FFA50 and FFA60%. Secondly, owing to significant gene-by-race interaction, associations were investigated separately in each of the two race groups. Linkage was tested with the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE gene. RESULTS: There were no race differences in the allele frequencies of the C-60G polymorphism of the LIPE gene. No association or gene-by-race interaction was observed in men. However, in women, strong gene-by-race interactions were observed for BMI (P=0.0005), FAT (P=0.0007), %FAT (P=0.0003), SF8 (P=0.0001), ASF (P=0.03) and ATF (P=0.01). When the analysis was performed separately in each race, white women carriers of the -60G allele exhibited lower %FAT (P=0.005) and SF8 (P=0.01) than non-carriers, while in black women, the -60G allele was associated with higher BMI (P=0.004), FAT (P=0.009), %FAT (P=0.01) and SF8 (P=0.0009). These associations were no longer significant after adjusting for INS. Evidence of linkage was observed in whites with ATF, FFAR, FFA50 and FFA60%. CONCLUSION: These results suggest that the C-60G polymorphism in the LIPE gene plays a role in determining body composition and that its effect is sex-, race- and insulin-dependent.

Abdomen↗

Is adiposity at normal body weight relevant for cardiovascular disease risk?

OBJECTIVE: To examine the relation between adiposity and risk factors for cardiovascular disease (CVD) in normal weight (NW) individuals. METHODS: Cross-sectional study using the sample of white people, aged from 17 to 60 y from the Québec Family Study and the Heritage Family Study. NW subjects with a body mass index (BMI) between 18.5 and 25 kg/m(2) (181 males and 265 females) and overweight (OW) subjects with a BMI between 25 and 30 kg/m(2) (133 males and 114 females) were retained for this study. NW subjects were divided into quintiles of each adiposity variable, then the quintiles and the OW group were evaluated for the presence of CVD risk factors. Using logistic regression analysis, the odds ratio (OR) for the prevalence of risk factors for each quintile of each adiposity variable and the OW group was estimated relative to the first quintile in NW subjects. Mean values of adiposity variables were compared between the subjects with and without risk factors. In these analyses, age and study cohort effects were taken into account. MEASUREMENTS: Percentage body fat (%fat) and fat mass (FM) measured by underwater weighing were available as adiposity variables. Risk factors included systolic and diastolic blood pressure, LDL and HDL cholesterol, triglycerides and fasting glucose. RESULTS: Wide ranges of values were observed for adiposity variables. HDL cholesterol, triglycerides and fasting glucose in NW males and HDL cholesterol in NW females were significantly correlated with all adiposity variables. For males, higher quintiles of adiposity variables in the NW group and the OW group tended to have higher ORs compared to the first quintiles for the risk factor variables. The fifth quintiles of all adiposity variables had the highest ORs (3.15 for %fat and 3.77 for FM) and they were significantly different from the first quintiles. OW males had ORs similar to those of the fifth quintiles for the risk factor variables. On the other hand, for females, the relatively linear associations were less clear in the NW group. In NW males, the subjects with at least one risk factor had significantly higher %fat and FM than the subjects without risk factors. In NW females, no significant difference was observed for these adiposity variables between the subjects with and without risk factors. CONCLUSION: NW males with elevated adiposity had higher prevalence of risk factors than NW males with less adiposity and the prevalence in the former was rather similar to that seen in OW males. On the other hand, measures of adiposity added little additional information to the BMI classification of NW on CVD risk factors in females.

Adipose Tissue↗

The effect of sex, age and race on estimating percentage body fat from body mass index: The Heritage Family Study.

OBJECTIVE: To study the effects of sex, age and race on the relation between body mass index (BMI) and measured percent body fat (%fat). DESIGN: Cross-sectional validation study of sedentary individuals. SUBJECTS: The Heritage Family Study cohort of 665 black and white men and women who ranged in age from 17 to 65 y. MEASUREMENTS: Body density determined from hydrostatic weighing. Percentage body fat determined with gender and race-specific, two-compartment models. BMI determined from height and weight, and sex and race in dummy coded form. RESULTS: Polynomial regression showed that the relationship between %fat and BMI was quadratic for both men and women. A natural log transformation of BMI adjusted for the non-linearity. Test for homogeneity of log transformed BMI and gender showed that the male-female slopes were within random variance, but the intercepts differed. For the same BMI, the %fat of females was 10.4% higher than that of males. General linear models analysis of the women's data showed that age, race and race-by-BMI interaction were independently related to %fat. The same analysis applied to the men's data showed that %fat was not just a function of BMI, but also age and age-by-BMI interaction. Multiple regression analyses provided models that defined the bias. CONCLUSIONS: These data and results published in the literature show that BMI and %fat relationship are not independent of age and gender. These data showed a race effect for women, but not men. The failure to adjust for these sources of bias resulted in substantial differences in the proportion of subjects defined as obese by measured %fat.

Adipose Tissue↗

Variability in the response of HDL cholesterol to exercise training in the HERITAGE Family Study.

In the HERITAGE Family Study, 675 sedentary, healthy, white and black men and women, aged 17 to 65 years, performed 20 weeks of supervised cycle ergometer exercise at the same relative intensity and weekly volume. As a group, subjects had normal mean baseline lipid levels for North Americans with the exception of below average high density lipoprotein cholesterol (HDL-C) levels. A significant mean increase in plasma HDL-C of 3.6 % was observed; however, there was marked variability in responsiveness to training, ranging from a mean 9.3 % decrease in Quartile 1 of HDL-C response to a mean 18 % increase in Quartile 4 (P < 0.0001 by ANOVA). Parallel changes in HDL(2)-C and HDL(3)-C, apolipoprotein A-I levels, and lipoprotein lipase activity were noted across quartiles. The change in HDL-C across quartiles was inversely related to baseline HDL-C (p < 0.0001) and to changes with training in plasma triglycerides (p = 0.0007). No significant differences in HDL-C response were observed across quartiles by sex, race, age, or increase in VO(2)max with training; however, weak positive associations were observed with age-adjusted education level and with reduction in abdominal fat and increase in VO(2)max at the ventilatory threshold following training. Multivariate regression analysis including baseline variables and training responses only accounted for 15.5 % of the variability in the HDL-C response to training. Thus, marked variability was found in the HDL-C response to the same endurance exercise training stimulus with only a modest amount of the response predictable by identified nongenetic factors.

Adaptation, Physiological↗

Race differences in the response of postheparin plasma lipoprotein lipase and hepatic lipase activities to endurance exercise training in men: results from the HERITAGE Family Study.

Endurance exercise training is known to produce favorable changes in the metabolic profile including reduced plasma triglyceride (TG) and increased high-density lipoprotein (HDL) cholesterol concentrations. These metabolic improvements are likely to contribute to the reduced coronary heart disease (CHD) risk often observed in physically active individuals. However, the physiological mechanisms responsible for such improvements in TG and HDL cholesterol concentrations with endurance exercise are not fully understood. The effect of a 20-week endurance exercise training program on plasma lipoproteins as well as on post-heparin plasma lipoprotein lipase (PH-LPL) and hepatic lipase (PH-HL) activities were therefore examined in a sample of 200 White and 69 Black men who were part of the HERITAGE Family Study. As expected, there were decreases in adiposity and in abdominal fat accumulation following training in both White and Black men. We also found that exercise training was associated with decreases in plasma cholesterol, TG and apolipoprotein B levels, as well as with an increase in HDL cholesterol concentrations in White men. In contrast, Black men showed an increase only in HDL(2) cholesterol over the 20-week period. Higher PH-LPL and lower PH-HL activities were noted in both ethnic groups at follow-up. Whereas in White men improvement of the lipoprotein-lipid profile was related to increased PH-LPL activity, no association between PH-LPL (or PH-HL) and lipoprotein-lipid variables was observed in Black men. Results of the present study suggest that in Whites, the increase in PH-LPL activity in response to endurance exercise training is associated with a better lipoprotein-lipid profile, therefore reducing CHD risk. However, the generally better metabolic profile of Black individuals may minimize further improvement of lipoprotein-lipid concentrations by exercise training.

Adipose Tissue↗

Familial resemblance for glucose and insulin metabolism indices derived from an intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family Study.

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a complex disease primarily caused by impairment in insulin sensitivity (SI) and insulin secretion. While a strong genetic component for T2DM is well established, there are few reports on racial differences in the magnitude of the genetic effects of T2DM and indices of glucose and insulin metabolism. We report here on the familial resemblance for traits related to glucose metabolism at pre-exercise training levels in 492 members from 99 sedentary White families and 259 members from 108 Black families participating in the multicenter HERITAGE Family Study. All these traits were obtained from the frequently sampled intravenous glucose tolerance test (IVGTT). They include glucose disappearance index (Kg), an overall index for glucose tolerance, acute insulin response to glucose (AIR(Glucose)) which is an index for insulin secretion, and those derived from the minimal model including SI and the disposition index (DI). DI, derived as the product of SI and AIR(Glucose), is a measure of the activity of the B-cells adjusted for insulin resistance. After adjustment for age, sex, and body mass index, the maximal heritability estimates in Blacks (Whites) are 48+/-14% (25+/-8%) for Kg, 44+/-14% (46+/-8%) for AIR(Glucose), 38+/-12% (44+/-8%) for SI and 32+/-14% (24+/-8%) for DI. Interestingly, Blacks have higher heritability for overall glucose tolerance than Whites but there is no race difference in heritability estimates for insulin sensitivity or insulin secretion.

Adult↗

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not associated with training-induced changes in body composition: The HERITAGE Family Study.

OBJECTIVE: To investigate the association between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and changes in body composition in response to endurance training. RESEARCH METHODS AND PROCEDURES: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat-free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre- and post-training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. RESULTS: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training-induced changes for any of the body composition phenotypes in both men and women. DISCUSSION: These results suggest that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not related to changes in body composition in response to exercise training.

Adipose Tissue↗

Changes in blood lipids consequent to aerobic exercise training related to changes in body fatness and aerobic fitness.

The contribution of changes in body fatness and aerobic fitness to changes in blood lipids after aerobic exercise training was investigated. The sample included 295 men (77 black, 218 white) and 355 women (131 black, 224 white), aged 17 to 65 years, from the HERITAGE Family Study. Participants underwent measurements at baseline and after 20 weeks of supervised exercise training on a cycle ergometer. Body fat mass (FM, in kilograms) was determined by underwater weighing, and aerobic fitness (maximal oxygen uptake, VO(2max), in milliliters per minute) was assessed by cycle ergometry. Blood lipid measurements included fasting plasma levels of high-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (CHOL), CHOL/HDL, and triglycerides (TG). A composite lipid change index (LCI) was derived by subjecting the Delta scores for the individual blood lipids to principal components analysis. The exercise training was accompanied by a mean increase of 17.5% in VO(2max) and a mean decrease of 3.3% in FM. Partial correlations, controlled for age, between absolute changes in VO(2max) and changes in the blood lipids were consistently low and nonsignificant. On the other hand, absolute changes in FM were significantly (P <.05) associated with changes in HDL-C (r = -.23), HDL(2)-C (r = -.17), and CHOL/HDL (r =.24) and the LCI (r = -.27) in men and with changes in LDL-C (r =.22), CHOL (r =.19), and CHOL/HDL (r =.15) and the LCI (r = -.19) in women. Forward stepwise regression confirmed that the change in FM was a better predictor of changes in blood lipids than the change in VO(2max), entering as a predictor in 4 of 8 regressions in both men and women. Change in VO(2max) did not enter as a significant predictor in any regression. Further, there were no differences in LCI between the upper and lower quartiles of VO(2max) change. On the other hand, there were significant differences between the low and high quartiles of FM change. No race effects were observed in any of the relationships, except that race was a significant predictor of changes in TG in both men and women. In conclusion, changes in blood lipids associated with aerobic exercise training do not appear to be related to changes in aerobic fitness per se; rather, they are weakly to moderately associated with changes in body fatness.

Adipose Tissue↗

Race differences in the pattern of familial aggregation for dehydroepiandrosterone sulfate and its responsiveness to training in the HERITAGE Family Study.

Using a familial correlation model to assess familial influences, baseline dehydroepiandrosterone sulfate (DHEAS) and its change (post-training minus baseline) in response to a 20-week endurance exercise training program were analyzed in 85 black families who participated in the HERITAGE Family Study (HERITAGE). Baseline levels were adjusted for a polynomial in age, and the training response was adjusted for a polynomial in age, as well as the baseline values, within 4 sex-by-generation groups before genetic analysis. We found that the maximal heritability for baseline DHEAS reached 66% (with no sex and generation differences) in black families, which is slightly (but not significantly) higher than the estimate (58%) reported previously in 99 white families in HERITAGE. Whereas weak, but significant, familial effects (26%) for the training response were previously reported for whites in HERITAGE, they were undetectable in the present study. Furthermore, we found heterogeneity in the pattern of familial aggregation (primarily due to different spouse and parent-offspring correlations) for both the baseline and its training response between blacks and whites. In conclusion, baseline DHEAS levels in blacks were also determined by substantial familial factors (just as for whites), independent of the effects of age and sex. Genetic and nongenetic familial components influencing baseline DHEAS levels in both races may be different.

Adolescent↗

Relationship of changes in maximal and submaximal aerobic fitness to changes in cardiovascular disease and non-insulin-dependent diabetes mellitus risk factors with endurance training: the HERITAGE Family Study.

The purpose of this study was to determine the relationship between changes in maximal oxygen uptake (VO2 max) and submaximal markers of aerobic fitness and changes in risk factors for cardiovascular disease (CVD) and non-insulin-dependent diabetes mellitus (NIDDM) consequent to a 20-week endurance training program. The 502 participants in this study were healthy and previously sedentary men (n = 250) and women (n = 252) of varying age (17 to 65 years) and race (blacks n = 142; whites n = 360) who had completed the HERITAGE Family Study testing and training protocol. Following baseline measurements, participants trained on cycle ergometers 3 days/week for a total of 60 exercise sessions starting at the heart rate (HR) associated with 55% of VO2 max for 30 minutes/session. This was progressively increased to the HR associated with 75% of VO2 max for 50 minutes/session, which was maintained during the last 6 weeks. VO2 max, heart rate at 50 W, power output at 60% of VO2 max, lipids and lipoproteins, resting blood pressure, body composition including abdominal fat (computed tomography [CT] scan), and blood glucose and insulin at rest and at peak following an intravenous glucose tolerance test (IVGTT) were determined both before and after training. Following training, there were significant increases in VO2 max (16%) and the power output at 60% of VO2 max and a significant decrease in HR at 50 W. These changes in markers of aerobic fitness were significantly correlated only to the changes in the body composition variables and the lipids and lipoproteins. Further, there was considerable individual variation in response for all variables studied. Finally, when risk factor data were analyzed by quartile of change in VO2 max, there were few significant relationships. It is concluded that there is a significant relationship between changes in markers of aerobic fitness and changes in several risk factors for CVD and NIDDM. However, the magnitude of these relationships is small.

Adolescent↗

Genome-wide linkage scan to detect loci influencing levels of dehydroepiandrosterones in the HERITAGE Family Study.

A genome-wide linkage scan was performed to identify genomic regions that influence levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and DHEA fatty acid esters (DHEA-FA) at baseline and in response to 20 weeks of endurance exercise training in sedentary white and black participants in the HERITAGE Family Study. The baseline levels were log-transformed and adjusted for the effects of age and sex prior to genetic analysis. The training responses were adjusted for the effects of age, sex, and the baseline values. A total of 509 autosomal component polymorphic markers were used for the genome scan with an average spacing of 6.0 Mb. Multipoint variance components linkage analyses were performed in nuclear families containing 360 white and 106 black sibling pairs. We found 5 genomic regions with significant linkages for baseline DHEA-FA in whites, with log odd (LOD) scores over 3.6 (P < 2 x 10(-5)). They include (1) D1S468 (LOD 4.56, 2.533 Mb, 1p36.22); (2) D2S177 (LOD 5.65, 52.663 Mb, 2p16.3); (3) D4S2397 (LOD 3.98, 32.246 Mb, 4p15.2); (4) the paraoxonase loci (LOD 3.93 approximately 3.99, 101.544 approximately 102.933 Mb, 7q21.3), and D7S821 (LOD 3.88, 104.497 Mb, 7q22.1); and (5) D12S372 (LOD 4.66, 2.129 Mb, 12q13.33). In addition, we obtained evidence of suggestive linkages (2.2 < LOD < 3.6; 2 x 10(-5) < P < 7 x 10(-4)) on chromosomes 3p, 6q, and 8q for baseline DHEAS; on chromosomes 2q, 3p, 9q, 10p, 16q, and 17p for baseline DHEA-FA in whites; and on chromosomes 9q and 11p for baseline DHEA in blacks. This is the first genome-wide linkage scan searching for genomic regions influencing human DHEA levels. Several potential candidate genes are located in these genomic regions, which warrant further studies in HERITAGE and other cohorts.

Adult↗

Changes in ventilatory threshold with exercise training in a sedentary population: the HERITAGE Family Study.

UNLABELLED: The purpose of this study was to evaluate the effect of exercise training intensity relative to the ventilatory threshold (VT) on changes in work (watts) and VO2 at the ventilatory threshold and at maximal exercise in previously sedentary participants in the HERITAGE Family Study. We hypothesized that those who exercised below their VT would improve less in VO2 at the ventilatory threshold (VO2vt) and VO2max than those who trained at an intensity greater than their VT. Supervised cycle ergometer training was performed at the 4 participating clinical centers, 3 times a week for 20 weeks. Exercise training progressed from the HR corresponding to 55% VO2max for 30 minutes to the HR associated with 75% VO2max for 50 minutes for the final 6 weeks. VT was determined at baseline and after exercise training using standardized methods. 432 sedentary white and black men (n = 224) and women (n = 208), aged 17 to 65 years, were retrospectively divided into groups based on whether exercise training was initiated below, at, or above VT. RESULTS: 1) Training intensity (relative to VT) accounting for about 26% of the improvement in VO2vt (R2 = 0.26, p < 0.0001). 2) The absolute intensity of training in watts (W) accounted for approximately 56% of the training effect at VT (R2 = 0.56, p < 0.0001) with post-training watts at VT (VT(watts)) being not significantly different than W during training (p > 0.70). 3) Training intensity (relative to VT) had no effect on DeltaVO2max. These data clearly show that as a result of aerobic training both the VO2 and W associated with VT respond and become similar to the absolute intensity of sustained (3 x /week for 50 min) aerobic exercise training. Higher intensities of exercise, relative to VT, result in larger gains in VO2vt but not in VO2max.

Adolescent↗

Cardiac output and stroke volume changes with endurance training: the HERITAGE Family Study.

PURPOSE: The purpose of this study was to determine the magnitude of changes in cardiac output (Qc), stroke volume (SV), and arterial-mixed venous oxygen difference (a-vO2 diff) during submaximal exercise following a 20-wk endurance training program, with the primary focus on identifying differences in response by race, sex, and age. METHODS: The participants in this study (N = 631) were healthy and previously sedentary men (N = 277) and women (N = 354) of varying age (17-65 yr) and race (blacks, N = 217; whites, N = 414) who had completed the HERITAGE Family Study protocol. After baseline measurements, participants trained on cycle ergometers 3 d x wk(-1) for a total of 60 exercise sessions starting at the HR associated with 55% of maximal oxygen uptake (VO2max) for 30 min/session and building to the HR associated with 75% of VO2max for 50 min/session, which was maintained during the last 6 wk. HR, Qc (CO2 rebreathing), and SV (Qc/HR) were determined in duplicate at 50 W and at 60% of VO2max on two different days both before and after training. RESULTS: After training, there were significant decreases in HR and Qc, and significant increases in SV and a-vO2 diff at 50 W (except for no change in a-vO2 diff in black men). The changes in HR differed by sex and age, and the changes in SV, Qc, and a-vO2 diff differed by race. Qc decreased by 0.6 L x min(-1) at 50 W for the total sample, consistent with the decrease in VO2 at this power output. At 60% of VO2max HR decreased, and SV, Q, and a-VO2 diff increased. There were small differences in response by sex (HR and SV), race (HR), and age (HR and Qc). CONCLUSION: It is concluded that the cardiovascular systems of men and women, blacks and whites, and younger and older subjects are not limited in their ability to adapt to endurance training.

Adolescent↗