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C Bouchard

Publications and source records attributed to C Bouchard.

At least 73 records · Page 4Linked to original sources
PubMed1997

Genetics of human obesity: recent results from linkage studies.

Excess body fat or body mass relative to height aggregates in families. It is commonly recognized that this familial aggregation of human obesity is accounted for in part by a significant genetic component. Thus the genetic heritability of the obesity phenotypes accounts for approximately 25-40% of the age- and gender-adjusted phenotypic variances. There is also growing evidence that single-gene effects can be detected under appropriate conditions. The focus of research has now shifted to candidate genes and DNA markers of various obesity phenotypes. To date, linkage results have been published from the Pima Indian Study, the San Antonio Family Heart or Diabetes Studies, the Paris Cohort of Obese Siblings, the University of Pennsylvania Family Obesity Study and the Quebec Family Study. The only genomic scan (with approximately 600 markers) reported to date is that from the Pima Indian sibling study. In that study, the strongest evidence for linkage with body fat was with markers on chromosome 11q, 6p and 3p. Evidence for linkage with markers on 7q was obtained in all family studies with the only apparent exception being the Pima Indians. Our own results from the Quebec Family Study suggest that there are linkages between body fat, as assessed from hydrodensitometry, and markers on 1p32-p22. Other linkages have been reported in the past but they are generally based on smaller sample size and weaker evidence.

Animals↗
PubMed1997

Genetics of human obesity: research directions.

Rapid strides in understanding the physiology controlling energy or nutrient intake and energy expenditure have complemented the search for the genetic basis of obesity. Several single gene defects are known that produce obesity in animals. All of these have been cloned within the past 4 years, providing a rich new base for understanding obesity. Since obesity is likely to be "multifactorial," a number of laboratories have used the quantitative trait locus (QTL) technique of genome scanning to identify candidate genomic regions and, eventually, genes that may influence body weight and body fat. So far, 18 QTLs have been identified in association with crossbreeding strains of mice or rats with variable susceptibility to obesity. A number of mendelian disorders are known to exist in humans, but no specific genes have yet been identified for them. The potential for inserting new genetic material into mammals has produced numerous transgenic mice with increased or decreased quantities of body fat. These models will provide a continuing source of new insights into obesity. Several areas in the human genome have been linked to the development of obesity. Among the candidate genes with evidence of linkage to body fat are TNF-alpha, adenosine deaminase, and melanocortin-3 receptor. The new insights described above have invigorated the pharmaceutical industry to increase their efforts for new drug development aimed at the growing problem of obesity.

Adipose Tissue↗
PubMed1997

Monitoring high-intensity endurance exercise with heart rate and thresholds.

Ventilatory and lactate thresholds have been proposed as tools to establish the highest steady-state intensity sustainable during prolonged physical exercise. The purposes of this study were to clarify whether the intensity at the ventilatory threshold could be sustained during prolonged high-intensity exercise and if the corresponding work rate, pulmonary ventilation, and blood lactate concentration could also be maintained. Fifteen young and healthy male subjects were submitted to a VO2max test on ergocycle and a 90-min high-intensity ergocycle endurance exercise test. During the 90-min exercise test, subjects were able to maintain an intensity corresponding to a heart rate 5 beats.min-1 lower than that predetermined from the ventilatory threshold. Heart rate, FeO2, and FeCO2 were stable during the period from 20 to 80 min, VO2 was constant from 30 to 80 min, while work output, pulmonary ventilation, blood lactate, and VCO2 decreased significantly over the 90-min performance. These results show that physiological parameters near the ventilatory threshold are not interchangeable and that some cannot be used to monitor high-intensity long term exercise. Moreover, they clearly demonstrate that the blood lactate concentration fluctuates substantially during a 90-min endurance performance and cannot predict the highest work intensity that can be sustained during prolonged exercise without fatigue. However, heart rate and VO2 at the ventilatory threshold seem to be more suitable markers for that purpose.

Adult↗
PubMed1997

Body composition by DEXA in older adults: accuracy and influence of scan mode.

Dual energy x-ray absorptiometry (DEXA) measures bone mineral content (BMC), bone mineral density (BMD), fat-free mass (FFM), and provides estimates of percent body fat. Changes in scan mode geometry (pencil beam vs array) may impact these measures and body composition estimates using multi-compartment models. Forty-one adults, ages 59-79 yr, were scanned in each mode and also underwent hydrostatic weighing and measurement of total body water (tritiated water dilution). The effect of scan mode on measurement of DEXA BMC, BMD, FFM, and percent body fat (DEXA %Fat) was examined. The effect of scan mode on percentage body fat determined by a 4-compartment body composition model (4 Comp %Fat) and comparison of DEXA %Fat and 4 Comp %Fat were also examined. BMC and DEXA %Fat were greater (1.3% and 3.9%, respectively, P < 0.01), and BMD and FFM were lower (1.1% and 1.9%, respectively, P < 0.01) with the array scan mode. The 4 Comp %Fat was significantly greater (0.2%) when the array scan mode measurements of total body bone mineral were used; however, these differences were physiologically inconsequential. Comparison between DEXA %Fat and 4 Comp %Fat measures revealed a total error of +/-5.0% in the older adults examined. These results indicate significant scan mode differences in total body BMC, BMD, FFM, and DEXA %Fat measurements and demonstrate the importance of using a single DEXA scan mode for clinical investigation, particularly with longitudinal studies. For all investigations with DEXA, the scan mode should be reported. Furthermore, the error associated with using DEXA alone to estimate percent fat in an older population suggests that this technique is unacceptable in a research setting.

Absorptiometry, Photon↗
PubMed1997

Muscle-specific creatine kinase gene polymorphism and VO2max in the HERITAGE Family Study.

This study examined the association between a DNA polymorphism in the muscle-specific creatine kinase (CKMM) gene and VO2max in the sedentary state, as well as its response (deltaVO2max) to a standardized 20-wk endurance training program. The subjects were 160 biologically unrelated Caucasian parents (80 women, 80 men) and 80 biologically unrelated adult offspring of the HERITAGE Family Study. The CKMM polymorphism was detected by PCR and digestion with the NcoI restriction enzyme. VO2max was measured during maximal cycle ergometer tests. VO2max was 2119 +/- 45 mL x min(-1) (mean +/- SE) or 26 +/- 0.4 mL x kg(-1) x min(-1). Both sexes had a significant (P < 0.05) increase in the deltaVO2max (women = 283 +/- 20 mL x min[-1] and men = 363 +/- 25 mL x min[-1]). Allele and genotype frequencies were not significantly different (P > 0.05) between sexes. Age and sex adjusted VO2max was significantly (P = 0.007) associated with the CKMM genotype in the parents, whereas no association (P > 0.05) was observed in the offspring. DeltaVO2max values adjusted for age, sex, VO2max, and body mass were characterized by genotype differences in both parents (P = 0.0004) and offspring (P = 0.0025). A significantly (P < 0.05) lower deltaVO2max to endurance training was detected in both parents and offspring homozygotes for the rare allele. The genotype accounted for at least 9% of the variance in deltaVO2max. These results indicate that the NcoI polymorphism in the 3' untranslated region of the muscle-specific creatine kinase gene is associated with the deltaVO2max to endurance training.

Adult↗
PubMed1997

Muscle-specific creatine kinase gene polymorphisms in elite endurance athletes and sedentary controls.

The purpose of this study was to investigate the association between elite endurance athlete (EEA) status and two restriction fragment length polymorphisms (RFLPs) at the muscle-specific creatine kinase (CKMM) gene locus. Genomic DNA was extracted from white blood cells or lymphoblastoid cell lines of 124 unrelated Caucasian male EEA (VO2max > 73 mL.kg-1.min-1) and 115 unrelated Caucasian sedentary male controls (SCON). The genetic polymorphism at the CKMM locus was detected by the polymerase chain reaction and DNA digestion with the NcoI and TaqI restriction endonucleases. The allelic frequencies for the NcoI and TaqI RFLPs were not different (P > 0.05) between EEA and SCON subjects. The three expected genotypes for CKMM-NcoI (1170/1170 bp, 1170/985 + 185 bp, and 985 + 185/985 + 185 bp) and CKMM-TaqI (1170/1170 bp, 1170/1020 + 150 bp, and 1020 + 50/1020 + 150 bp) were observed in the EEA and SCON groups. These genotype frequencies were in Hardy-Weinberg equilibrium, but they were not significantly (P > 0.05) different between the EEA and SCON. A strong (P < 0.001) linkage disequilibrium was detected among the NcoI and TaqI RFLPs in both EEA and SCON. These findings indicate that the skeletal muscle CK-NcoI and CK-TaqI gene polymorphisms are not associated with the elite endurance athlete status.

Adult↗
PubMed1997

Absence of linkage between VO2max and its response to training with markers spanning chromosome 22.

An extensive search for linkage between DNA markers and the response of VO2max to training has recently been launched in the HERITAGE Family Study. This is the first report on a genome-wide search strategy to locate chromosomal regions and positional candidate genes for cardiorespiratory endurance phenotypes. Linkage between seven markers spanning chromosome 22 spaced approximately 10 cM apart (D22S264, D22S274, D22S301, D22S304, D22S421, IL2RB, and PDGFB) and VO2max at baseline, as well as its response to endurance exercise training, was examined using the sib-pair linkage method. Markers were genotyped in at least 210 sib-pairs derived from 128 adult brothers (25 +/- 6 yr; mean +/- SD) and 138 sisters (24 +/- 6 yr) from 86 Caucasian families. VO2max, maximal heart rate, and maximal oxygen pulse were measured during stationary cycle tests before and after a standardized 20-wk endurance training program. On average, the initial VO2max was 2654 +/- 767 mL.min-1 while training increased VO2max significantly by 430 +/- 239 mL.min-1 or 16% (P < 0.0001). The VO2max response was adjusted for age and initial VO2max. No evidence of linkage was found between any of these markers on chromosome 22 and VO2max or its trainability.

Adolescent↗
PubMed1997

Familial aggregation of obesity, candidate genes and quantitative trait loci.

This brief review covers the findings reported in 1996 and in the first 2 months of 1997 on the genetic epidemiology and the molecular markers of human obesity. Although relatively little new evidence has been published on the heritability and other genetic epidemiology characteristics of obesity and fat topography, more has been reported on candidate genes, positional candidate genes and quantitative trait loci. Two recent genome-wide scans have revealed that several molecular markers on different chromosomes were linked to obesity-related phenotypes. Little support for a role for specific candidate genes can be found at this time. A large number of rodent quantitative trait loci have been uncovered so far but they have not yet been systematically tested in human populations.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Negative energy balance with exercise in identical twins: plasma glucose and insulin responses.

The effects of long-term (93 days) negative energy balance on plasma glucose and insulin were investigated by means of exercise with constant energy intake in seven pairs of young sedentary male identical twins. Results showed a significant decrease in fasting (-24%, P < 0.02) and postprandial insulin (-16%, P < 0.05). Fasting and postprandial plasma glucose and glucagon were not modified. Mean glucose disposal rate measured during a euglycemic-hyperinsulinemic clamp performed in five twin pairs was increased by 34% (P = 0.13). No significant intrapair similarity was found for the responses of fasting and postprandial insulin levels and of glucose disposal rate. Changes in glucose disposal rate were significantly greater in high compared with low losers for computerized tomography-measured abdominal visceral fat (3.0 +/- 1.1 vs. 0.3 +/- 0.5 mg x kg(-1) x min(-1), P < 0.05) despite similar losses in total body fat. We conclude that 1) a long-term negative energy balance generated by exercise training significantly reduces plasma insulin levels, whereas insulin sensitivity tends to be improved; 2) training-induced changes in insulin sensitivity are associated with changes in abdominal visceral fat; and 3) data from this experiment conducted with a small number of twin pairs suggest that the genotype does not seem to be a major determinant of the changes in insulin levels and sensitivity brought about by negative energy balance with exercise.

Abdomen↗
PubMed1997

Acute and chronic effects of exercise on leptin levels in humans.

The acute (single bout of exercise) and chronic (exercise training) effects of exercise on plasma leptin were investigated in 97 sedentary adult men (n = 51) and women (n = 46) participating in the HERITAGE Family Study. Exercise training consisted of a standardized 20-wk endurance training program performed in the laboratory on a computer-controlled cycle ergometer. Maximal oxygen uptake, body composition assessed by hydrostatic weighing, and fasting insulin level were also measured before and after training. Pre- and posttraining blood samples were obtained before and after completion of a maximal exercise test on the cycle ergometer. Exercise training resulted in significant changes in maximal oxygen uptake (increase in both genders) and body composition (reduction of fat mass in men and increase in fat-free mass in women). There were considerable interindividual differences in the leptin response to acute and chronic effects of exercise, some individuals showing either increase or reduction in leptin, others showing almost no change. On average, leptin levels were not acutely affected by exercise. After endurance training was completed, leptin levels decreased significantly in men (from 4.6 to 3.9 ng/ml; P = 0.004) but not in women. However, after the training-induced changes in body fat mass were accounted for, the effects of exercise training were no longer significant. Most of the variation observed in leptin levels after acute exercise or endurance training appears to be within the confidence intervals of the leptin assay. We conclude that there are no meaningful acute or chronic effects of exercise, independent of the amount of body fat, on leptin levels in humans.

Adolescent↗
PubMed1997

Familial resemblance of plasma lipids, lipoproteins and postheparin lipoprotein and hepatic lipases in the HERITAGE Family Study.

The familial aggregation of lipids and lipoproteins and plasma postheparin triglyceride lipases was investigated in 86 Caucasian families participating in the HERITAGE Family study, a study investigating the role of genetic factors in the adaptation to exercise training and its relationships with cardiovascular disease risk factors. Accordingly, sedentary subjects were recruited, tested for a battery of measurements, exercise trained for 20 weeks, and were re-measured. The present report includes plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides, and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities measured in 437 sedentary individuals (171 parents and 266 adult offspring) before training. Significant familial resemblance was observed for all the age-adjusted phenotypes. The pattern of familial correlations reveals no spouse correlations but significant parent-offspring and sibling correlations for total cholesterol, HDL-cholesterol and LDL-cholesterol with heritability (h2) estimates of 62%, 83%, and 50%, respectively. For plasma triglyceride concentrations (h2 = 55%) and HL activity (h2 = 40%), significant spouse correlations were found in addition to parent-offspring and sibling correlations, suggesting that common familial environment in addition to genetic factors contribute to the familial resemblance. For plasma LPL activity, there was no spouse correlation, but sex differences were found in the familial correlations with higher heritabilities in female pairs (h2 = 76%) compared to male pairs (h2 = 30%) and opposite-sex pairs (h2 = 44%). These results confirm the findings of previous family studies showing that genetic factors are major determinants of the familial resemblance in plasma lipids and lipoproteins and suggest the presence of sex differences in the heritability of postheparin LPL activity.

Adolescent↗
PubMed1997

Cross-trait familial resemblance for body fat and blood lipids: familial correlations in the Quebec Family Study.

In an attempt to better understand the genetic basis of the metabolic syndrome, we have undertaken a series of studies on the familial aggregation in the clustering of the coronary heart disease risk factors which characterize this syndrome. In the present study, the hypothesis of shared genetic (pleiotropy) and/or environmental factors between body fat and blood lipids is investigated by examining cross-trait (eg, father's body fat with his son's blood lipid) familial resemblance between 4 indicators of body fat (body mass index [BMI], sum of 6 skin folds [SF6]) and fat distribution (the ratio of the trunk to extremity skin folds adjusted [TER-sf] and unadjusted [TER] for SF6), and 5 blood lipid variables (total cholesterol [CH], triglycerides [TG], cholesterol associated with high-density lipoproteins [HDL], the CH/ HDL ratio and the difference between CH and HDL [CH-HDL]) measured in 1239 individuals from 309 families participating in the Quebec Family Study. A bivariate correlation model was used to obtain maximum likelihood estimates of cross-trait spouse, parent-offspring, and sibling correlations after adjustment of body fat and lipid data for the effects of age, separately in the four sex-by-generation groups. Likelihood ratio tests revealed the presence of significant (P < .05) cross-trait resemblance between body fat (BMI and SF6) and all lipid traits except CH and also between fat distribution (TER and TER-sf) and CH/HDL and CH-HDL. Only sibling cross-trait correlations were significant for all body fat-lipid pairs of measures, with bivariate familiality estimates (i.e., shared genetic and/or environmental factors) ranging from 8% to 40%. Although the hypothesis of genetic pleiotropy cannot be ruled out from the pattern of cross-trait correlations found in the present study, we conclude that environmental factors shared within sibships are probably more important than common genes in determining the covariation between body fat and blood lipids.

Adolescent↗
PubMed1997

Glucose metabolism in identical twins discordant for obesity. The critical role of visceral fat.

Obesity, especially intraabdominally deposited fatness, is associated with reduced insulin sensitivity. However, it is not well established whether this association is confounded by genetic factors. We studied 23 monozygous twin pairs (14 female, 9 male), 33-59 yr old, who had, on the average, 18 kg intrapair difference in body weight. A 75-g oral glucose tolerance test with glucose and insulin measurements at 30-min intervals was performed, and fat distribution was determined with magnetic resonance imaging. The pairs were divided into two groups by the gender-specific median of the abdominal visceral fat area (AVF) in the obese co-twins. In the high-AVF pairs, the mean area under curve (AUC) for glucose (mmol x min/L) was 758 vs. 968 (P = 0.001), AUC for insulin (mU x min/L) was 4320 vs. 8741 (P = 0.001), and insulin sensitivity index (mg x L x L/mmol x mU x min) was 71.5 vs. 45.9 (P < 0.001) in the lean and obese co-twins, respectively. In the low AVF pairs, the mean AUC for glucose was 669 vs. 706 (not significant), AUC for insulin was 3323 vs. 4241 (not significant), and the sensitivity index was 85.2 vs. 73.7 (P = 0.04) in the lean and obese co-twins, respectively. In subjects who are genetically identical but who are discordant for body mass, only those who differ most in visceral fat level are characterized by major alterations in insulin sensitivity and glucose tolerance.

Adipose Tissue↗
PubMed1997

Androstane-3alpha,17beta-diol glucuronide as a steroid correlate of visceral obesity in men.

Plasma levels of androstane-3alpha,17beta-diol glucuronide (3alpha-DIOL-G) and androsterone glucuronide (ADT-G) as well as testosterone and adrenal C19 steroid concentrations were measured in a sample of 80 men in whom visceral adipose tissue (AT) accumulation was also determined by computed tomography. Plasma 3alpha-DIOL-G concentrations showed significant positive correlations with total body fat mass (r = 0.31; P < 0.05) and percent body fat (r = 0.28; P < 0.05). Furthermore, plasma 3alpha-DIOL-G levels were significantly associated with visceral adipose tissue accumulation (r = 0.41; P < 0.0005) as well as fasting plasma insulin (r = 0.35; P < 0.005) and glycemic and insulinemic responses to an oral glucose load (r = 0.39; P < 0.0005 and r = 0.32; P < 0.005, respectively). However, associations between 3alpha-DIOL-G and plasma glucose-insulin homeostasis indexes were no longer significant after adjustment for visceral AT area. ADT-G levels were not significantly associated with any of the adiposity variables. Subjects matched for abdominal sc AT area but with either low or high levels of visceral AT area showed significant differences in 3alpha-DIOL-G concentrations (P < 0.05), whereas subjects with low or high levels of abdominal sc AT but similar levels of visceral AT had similar 3alpha-DIOL-G concentrations. Among men with high testosterone levels, subjects with reduced 3alpha-DIOL-G concentrations had lower visceral adipose tissue accumulation than subjects with increased 3alpha-DIOL-G levels. The present results indicate that plasma 3alpha-DIOL-G, but not ADT-G, is a steroid correlate of visceral obesity. Excess visceral adipose tissue and/or concomitant alterations in insulin levels or in vivo insulin action could be responsible for the increased 3alpha-DIOL-G formation observed in this condition.

Adipose Tissue↗
PubMed1997

Variation in plasma fibrinogen over one year: relationships with genetic polymorphisms and non-genetic factors.

We analyzed plasma fibrinogen level in relation to genetic polymorphisms in the alpha- and beta-fibrinogen gene loci. Furthermore, the association of other CVD risk markers with fibrinogen was studied twice, with a time interval of one year in 50 to 60 year old men (n = 183). DNA polymorphisms were detected by PCR and digestion with Taq I (alpha-fibrinogen), Hind III and Bcl I (beta-fibrinogen) restriction enzymes. The correlation coefficient between fibrinogen measurements was 0.48 (p < 0.001). Blood leucocytes and waist-to-hip circumference ratio were the strongest correlates of fibrinogen level in both examinations, and the changes in leucocyte count and plasma fibrinogen correlated positively (r = 0.40, p < 0.001). In Eastern Finnish men, the Taq I, Hind III or Bcl I restriction fragment length polymorphisms of the alpha- or beta-fibrinogen gene loci did not associate with fibrinogen level, either cross-sectionally or longitudinally.

Biomarkers↗
PubMed1997

[Sensitivity and specificity of thyreostimuline (TSH) determination on filter paper for the diagnosis of hypothyroidism in the elderly].

The aim of this study was to measure the prevalence of hypothyroidism in 239 elderly patients and to determine the validity of TSH assay on blood dried on filter paper (spot-test) for the diagnosis of hypothyroidism. The sensitivity and specificity of the spot-test were evaluated in a subgroup of 177 subjects. The prevalence of hypothyroidism was 14.2% (34/239). The spot-test did not give satisfactory results for the diagnosis of hypothyroidism in elderly subjects. Due to the lack of specificity, most of the positive results were false positives and the clinician had to rely on laboratory determination of plasma TSH level to confirm hypothyroidism in half of the patients. We do not recommend the spot-test for the diagnosis of hypothyroidism in the elderly. Laboratory assay of plasma TSH is required for confirming hypothyroidism in the elderly.

Aged↗