Publications

The Karvonen heart rate (HR) reserve formula has been used extensively to estimate the HR associated with a given %VO2max. However, there have been no studies with a large heterogeneous population to determine if this formula is accurate. Therefore, 663 subjects in the HERITAGE Family Study with complete data and a wide range of initial VO2max values were classified by age (17–29, 30–49, and 50–65 years), sex (male and female), race (black and white) and also grouped by their initial VO2max levels (ml/kg/min). Regression equations for HR to VO2 were calculated for each subject. HRs at 30%–100% VO2max were estimated from each regression equation. Using a paired t-test with significance set at 0.01, mean HRs at each %VO2max were compared with HRs estimated by the Karvonen formula. Women had higher resting (RHR) and higher submaximal HRs than men but their HRmax was not different. With increasing age, RHR was similar but HRmax decreased. There were no differences between blacks and whites for RHR or HRmax. For all subjects, for both sexes, for both races, for the 3 age groups and for the subjects grouped by their initial VO2max, there was a significant increase in VO2max and a significant decrease in HR at the same absolute VO2 (ml/min) after training but there was no difference in HR at the same %VO2max. The Karvonen formula gave higher estimates of HR at the same %VO2max (12–17, 9–14, 6–9 and 0–6 beats/min higher at 30%, 50%, 70% and 90% VO2max, respectively). It is concluded that the Karvonen formula is not accurate before and after training in a large heterogeneous population of men and women, blacks and whites of different ages and initial levels of fitness. Supported by NIH-NHLBI grants

PURPOSE: Aerobic exercise training provides numerous biological and physiological health benefits towards the prevention and treatment of various chronic diseases. However, not all individuals increase cardiorespiratory fitness (CRF) with exposure to a given dose of aerobic training: some individuals are highly trainable and increase CRF, while others respond poorly. Genetic background is known to contribute to interindividual variation in adaptations to aerobic training. Our current understanding of genetics and exercise is limited primarily to the nuclear genome as only a few laboratories have investigated the role of the mitochondrial genome. The purpose of this study was to determine whether mitochondrial DNA (mtDNA) sequence, heteroplasmy, and indels differed among individuals previously characterized as elite endurance athletes, and high- or low-responders to aerobic training. METHODS: DNA was isolated from whole blood in healthy subjects part of the GENATHLETE (world class endurance athletes; n=15) and HERITAGE (CRF response levels: high responders n=15; low responders n =15) study cohorts. mtDNA was amplified by long-range polymerase chain reaction, then tagged with Nextera libraries and sequenced on a Miseq instrument. Unique mtDNA sequence variants were called when at least two individuals in a group had the variant. RESULTS: Compared to athletes and high-responders, low-responders had unique mtDNA single nucleotide polymorphisms (SNPs) in D-loop (displacement-loop) hypervariable region (HVR) 2 at positions 72, 152, 185, 188, 228, 295, 462, and 489. Of the HVR2 positions, position 188 was unique only to low-responders. Indels were unique to athletes and high-responders and located in D-loop HVR1 (16179, 16182, 16188, 16192), HVR2 (302), and HVR3 (567) positions. mtDNA Heteroplasmy was not different between groups. CONCLUSIONS: Our results highlight an area of the mitochondrial genome responsible for DNA replication and transcription that may contribute to an individual's ability to improve CRF with aerobic training. Ongoing work aims to 1) confirm present findings in low responders through increasing sample size from the HERITAGE cohort, and 2) test for interactions between mitochondrial and nuclear genomes associated with response to a given dose of aerobic training.

DIONNE, F. T., L. TURCOTTE, M.-C., THIBAULT, M. R. BOULAY, J. S. SKINNER, and C. BOUCHARD. Mitochondrial DNA sequence polymorphism, VO2max, and response to endurance training. Med. Sci. Sports Exerc., Vol. 23, No. 2, pp. 177–185, 1991. Mitochondrial DNA sequence variation was determined in 46 sedentary young adult males who took part in ergocycle endurance training programs in two laboratories to assess whetther mitochondrial DNA variants were associated with individual differences in maximal oxygen uptake (VO2max) and its response to training. VO2max was obtained from a progressive ergocycle test to exhaustion. White blood cell mitochondrial DNA was characterized with the restriction fragment length polymorphism (RFLP) technique using 22 restriction enzymes and human mitochondrial DNA as a probe for hybridization. Multiple mitochondrial DNA variants were detected with 15 of the enzymes. Some subjects exhibited many RFLPs, while others showed no variation. These RFLPs (morphs) were generated by base substitutions located in gene regions coding for mitochondrial proteins as well as in the noncoding regions. Carriers of three mitochondrial DNA morphs, two in the subunit 5 of the NADH dehydrogenase gene and one in the tRNA for threonine, had a VO2max (ml.kg-1.min-1) in the untrained state significantly higher than noncarriers, while carriers of one mitochondrial DNA morph in subunit 2 of NADH dehydrogenase had a lower initial VO2max. Endurance training increased VO2max, by a mean of 0.51 of O2, with individual differences ranging from gains of 0.06 to 1.03. After adjustment for training site and initial VO2max, a lower response was observed for three carriers of a variant in subunit 5 of the NADH dehydrogenase detected with Hincil (mean gain of 0.28 l; P<0.05). These results suggest that sequence variation in mitochondrial DNA may contribute to individual difference in VO2max and its response to training.

No abstract is provided for this article.

Background C-reactive protein (CRP) concentrations have been found to be higher in premenopausal women than in men, whereas interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations have been reported to be lower in women than in men. Objective: The objective was to determine whether the sex difference in body fat distribution accounts for the observed sex differences in inflammatory markers. Design: Plasma CRP, IL-6, and TNF-α concentrations were measured in 208 healthy men (age: 42.2 ± 15.2 y) and in 145 healthy women (age: 36.8 ± 11.1 y). Results: Compared with men, premenopausal women had higher CRP concentrations [1.24 (25th percentile: 0.54; 75th percentile: 3.04) compared with 0.94 (0.51, 2.40) mg/L; P < 0.05] and lower plasma TNF-α concentrations [1.50 (25th percentile: 1.23; 75th percentile: 1.82) compared with 1.71 (1.40, 2.05) pg/mL; P < 0.001]. No sex difference in IL-6 concentrations was noted. Regression analyses indicated that the relation between CRP or IL-6 and visceral adipose tissue (VAT) and subcutaneous AT (SAT) was sex-specific; a significantly steeper slope was observed in women than in men (P < 0.05). Sex differences in CRP concentrations were abolished after SAT was adjusted for. In a multivariate model of the whole sample, we found that both SAT and VAT and the sex × SAT interaction term were significant correlates of CRP and IL-6 concentrations. Finally, whereas CRP concentrations were largely influenced by visceral adiposity in men, subcutaneous adiposity was the key correlate of CRP in women. Conclusion: The higher CRP concentrations found in women appear to be due to their greater accumulation of subcutaneous fat than that observed in men.

No abstract is provided for this article.

No abstract is provided for this article.

. Rosmond R, Ukkola O, Chagnon M, Bouchard C &amp; Björntorp P (Department of Heart and Lung Diseases, Göteborg University, Sweden; Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA; Department of Internal Medicine, University of Oulu, Oulu, Finland). Polymorphisms of the β 2 ‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men. J Intern Med 2000; 248: 239–244. Objective. To investigate the effect of polymorphisms in codon 16 (Arg16Gly) and codon 27 (Gln27Glu) of the β 2 ‐adrenergic receptor gene (ADRB2) on anthropometric, endocrine, metabolic and haemodynamic variables. Design. A cross‐sectional study. Subjects. A subgroup of 284 Swedish men from a population sample of 1040 at the age of 51 years. Main outcome measures. Genotype examination of ADRB2 polymorphisms in codon 16 and codon 27 with polymerase chain reaction and restriction fragment length polymorphism. Anthropometric measurements included body mass index, waist‐to‐hip ratio and abdominal sagittal diameter. Endocrine measurements included blood levels of testosterone, insulin‐like growth factor I, and leptin plus salivary cortisol. Overnight fasting values of serum insulin, blood glucose, triglycerides, total, low and high density lipoprotein cholesterol, as well as blood pressure and resting heart rate, were also determined. Results. Polymorphisms were frequent in both codon 16 and codon 27. The Arg16Gly genotype showed significant relationships to elevated central distribution of body fat and to systolic blood pressure, whilst the Glu27Glu genotype was associated with elevated leptin and triglyceride levels but not to other measurements, including obesity variables. Conclusions. We conclude that only a few cardiovascular risk factors are associated with DNA sequence variation in the ADRB2 in Swedish men.

Eating behaviour traits are associated with body weight variations in adults. The Three-Factor Eating Questionnaire (TFEQ) measures cognitive restraint, disinhibition and hunger, as well as their corresponding subscales, e.g. rigid and flexible control. The TFEQ has not been widely used in adolescents to investigate eating behaviour traits associated with body weight. The aim of the present study was to assess whether eating behaviour traits were associated with BMI in male and female adolescents. Sixty adolescents (thirty females and thirty males; mean age 15·0 ( sd 2·4) years) from the Québec Family Study completed the TFEQ and 3 d dietary records. There were no sex differences in the TFEQ scores. Rigid control, disinhibition and emotional susceptibility (to overeat) were positively related to BMI z -scores for the entire sample ( r 0·3, P &lt; 0·05). There was a positive relationship between BMI z -scores and rigid control ( r 0·39, P &lt; 0·05) in females, while BMI z -scores were positively related to emotional susceptibility ( r 0·42, P &lt; 0·02) and disinhibition ( r 0·41, P &lt; 0·03) in males. Adolescents characterised by both high disinhibition and high rigid control had significantly higher BMI z -scores than those by both low disinhibition and low rigid control. There were no significant differences in BMI z -scores between the flexible control categories. Dietary macronutrient content was not consistently related to eating behaviour traits. These results show that the eating behaviour traits of disinhibition and rigid control are independently related to BMI z -scores in this group of adolescents.

No abstract is provided for this article.

PURPOSE A genome-wide linkage scan was performed to identify genes affecting maximal heart rate (HRmax) and heart rate reserve (HRrsv) in the sedentary state and their responses to a standardized 20–week endurance training program. METHODS A total of 654 polymorphic markers were used and 353 pairs of siblings from 99 White nuclear families and 102 sibling pairs from 114 Black family units were available. HR was measured by ECG at rest and during maximal exercise and HRrsv was calculated as HRmax - resting HR. Baseline phenotypes were adjusted for age, sex and body mass index, and the training responses (post-training - baseline) were adjusted for age, sex, baseline BMI and baseline value of the response phenotype. Multi-point linkage analyses were done using both regression and variance components-based methods. RESULTS In Whites, baseline HRmax showed the strongest evidence of linkage (LOD=2.54, p=0.0003) with markers on chromosome 10p13. The maximum linkage was detected at 9.4 Mb from pter and a 1-LOD region covered about 7.2 Mb. HRrsv training response QTLs were detected on chromosomes 8q22-q23 (LOD=2.24, p=0.00065 at 107 Mb) and 20q13.1 (LOD=2.51, p=0.00034 at 43.9 Mb). In Blacks, strong evidence of linkage was found for baseline HRrsv on chromosome 7q35 (LOD=3.03, p=0.00009 at 143.2 Mb). CONCLUSIONS All these chromosomal regions include several potential candidate genes and therefore warrant further studies in the HERITAGE cohort and other studies.