Showing papers by "Claude Bouchard published in 2003"

The human gene map for performance and health-related fitness phenotypes: the 2005 update.

Abstract: The current review presents the 2005 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2005. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise, or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed, but a gene or locus must be supported by at least one positive study before being inserted on the map. By the end of 2000, in the early version of the gene map, 29 loci were depicted. In contrast, the 2005 human gene map for physical performance and health-related phenotypes includes 165 autosomal gene entries and QTL, plus five others on the X chromosome. Moreover, there are 17 mitochondrial genes in which sequence variants have been shown to influence relevant fitness and performance phenotypes. Thus, the map is growing in complexity. Unfortunately, progress is slow in the field of genetics of fitness and performance, primarily because the number of laboratories and scientists focused on the role of genes and sequence variations in exercise-related traits continues to be quite limited.

Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study.

Abstract: KATZMARZYK, P. T., A. S. LEON, J. H. WILMORE, J. S. SKINNER, D. C. RAO, T. RANKINEN, and C. BOUCHARD. Targeting the Metabolic Syndrome with Exercise: Evidence from the HERITAGE Family Study. Med. Sci. Sports Exerc., Vol. 35, No. 10, pp. 1703–1709, 2003. Purpose: To determine the efficacy of exercise training in treating the metabolic syndrome. Methods: The sample included 621 black and white participants from the HERITAGE Family Study, identified as sedentary and apparently healthy (no chronic disease or injury). The metabolic syndrome was defined as having three or more risk factors according to the guidelines of the National Cholesterol Education Program, including elevated waist circumference, blood pressure, triglycerides, blood glucose, and low HDL cholesterol. The presence of the metabolic syndrome and component risk factors were determined before and after 20 wk of supervised aerobic exercise training. Results: The prevalence of the metabolic syndrome was 16.9% in this sample (105/621) of apparently healthy participants. Of the 105 participants with the metabolic syndrome at baseline, 30.5% (32 participants) were no longer classified as having the metabolic syndrome after the exercise training. Among the 32 participants who improved their metabolic profile, 43% decreased triglycerides, 16% improved HDL cholesterol, 38% decreased blood pressure, 9% improved fasting plasma glucose, and 28% decreased their waist circumference. There were no sex or race differences in the efficacy of exercise in treating the metabolic syndrome: 32.7% of men, 28.0% of women, 29.7% of black, and 30.9% of white participants with the metabolic syndrome were no longer classified as having the syndrome after training. Conclusion: Aerobic exercise training in patients with the metabolic syndrome can be useful as a treatment strategy and provides support for a role for physical activity in the prevention of chronic disease.

Obesity – is it a genetic disorder?

Abstract: Obesity is one of the most pressing problems in the industrialized world. Twin, adoption and family studies have shown that genetic factors play a significant role in the pathogenesis of obesity. Rare mutations in humans and model organisms have provided insights into the pathways involved in body weight regulation. Studies of candidate genes indicate that some of the genes involved in pathways regulating energy expenditure and food intake may play a role in the predisposition to obesity. Amongst these genes, sequence variations in the adrenergic receptors, uncoupling proteins, peroxisome proliferator-activated receptor, and the leptin receptor genes are of particular relevance. Results that have been replicated in at least three genome-wide scans suggest that key genes are located on chromosomes 2p, 3q, 5p, 6p, 7q, 10p, 11q, 17p and 20q. We conclude that the currently available evidence suggests four levels of genetic determination of obesity: genetic obesity, strong genetic predisposition, slight genetic predisposition, and genetically resistant. This growing body of research may help in the development of anti-obesity agents and perhaps genetic tests to predict the risk for obesity.

The Human Obesity Gene Map: The 2002 Update

Abstract: This is the ninth update of the human obesity gene map, incorporating published results through October 2002 and continuing the previous format. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) from human genome-wide scans and various animal crossbreeding experiments, and association and linkage studies with candidate genes and other markers is reviewed. For the first time, transgenic and knockout murine models exhibiting obesity as a phenotype are incorporated (N = 38). As of October 2002, 33 Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and the causal genes or strong candidates have been identified for 23 of these syndromes. QTLs reported from animal models currently number 168; there are 68 human QTLs for obesity phenotypes from genome-wide scans. Additionally, significant linkage peaks with candidate genes have been identified in targeted studies. Seven genomic regions harbor QTLs replicated among two to five studies. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 222 studies reporting positive associations with 71 candidate genes. Fifteen such candidate genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. More than 300 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful sites can be found at http://obesitygene.pbrc.edu.

Do 6-y changes in eating behaviors predict changes in body weight? Results from the Québec Family Study.

Abstract: OBJECTIVE: This study was performed to examine changes in eating behaviors as assessed by the three-factor eating questionnaire (TFEQ) and to quantify the potential associations between these eating behaviors and body weight changes in a 6-follow-up study. DESIGN AND SUBJECTS: Prospective study performed in men and women who were tested twice (Visit 1=1989–1995 and Visit 2=6 y later) in the Quebec Family Study (QFS). RESULTS: Women were more restrained and less hungry than men. To reduce food intake, women relied more on strategic dieting behavior and avoided more fattening food. However, they had higher emotional and situational susceptibility to eat than men. Significant decreases in the disinhibition score were noted over time in women (P<0.01), which resulted from a decrease in habitual susceptibility behavior to increase food intake. In men, we observed an increase in the avoidance of fattening food (P<0.05). In both genders, we found that the 6-y change in restraint behavior was negatively correlated with body weight changes (P<0.05). In women, a high restraint behavior seems to promote weight gain, whereas in men, it is associated with the opposite trend. CONCLUSION: These results suggest that variables reflecting some eating behaviors are associated with body weight changes in a free-living context. However, these behaviors are expressed differently between men and women. These behaviors should be considered in clinical interventions for individuals seeking a better body weight control.

Genome-Wide Linkage Scan for the Metabolic Syndrome in the HERITAGE Family Study

Abstract: 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 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.

Handbook of Obesity: Clinical Applications

Abstract: Handbook of Obesity: Clinical Applications, Third Edition is the premier reference for physicians and researchers in the field of obesity. Written by leading scientists and clinicians, this handbook offers unparalleled depth and breadth of coverage concerning this growing global and chronic disease that affects and exacerbates comorbid conditions including diabetes and heart disease. This Third Edition is full of many revisions including: The sections Etiology and Pathophysiology have been updated to reflect state-of-the-art advancements in the prevalence, etiology, and pathophysiology of obesity New chapters have been added and revisions made to the subjects of genetics, molecular biology, endocrine determinants of obesity, the metabolic syndrome, and the relationship between obesity and diabetes Written by the field's leading scientists and clinicians, Handbook of Obesity: Clinical Applications, Third Edition: has unparalleled coverage of the full range of subjects comprising the field of obesity. is packed with charts, diagrams, and tables that conveniently summarize key information and concepts elucidates state-of-the-art knowledge of the definition, prevalence, etiology, and pathophysiology of obesity

Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort.

Abstract: Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) DNA sequence variants were determined in 96 unrelated female subjects with severe obesity (mean body mass index [BMI], 42.3 kg/m2) and in 96 non-obese female controls (mean BMI, 23.0 kg/m2) from the Swedish Obese Subjects (SOS) cohort. A single base substitution (T45G) at codon 15 of exon 2 resulting in no change in amino acid (Gly15Gly) was found in equal frequencies among obese and control subjects. However, this polymorphism was associated with serum cholesterol and waist circumference (P=.023 and.043, respectively) in the obese group. A IVS2 + G62T sequence variation was also identified, but had similar prevalence rates in obese and control subjects. Blood glucose was highest in the obese female subjects who were homozygotes for the G allele (GG) of the IVS2 + G62T polymorphism (N=56; P=.033) and all the diabetics (n=6) in this sample were in this group. IVS2 + G62T polymorphism was also associated with BMI (P=.014), diastolic blood pressure (P=.009), and sagittal diameter (P=.032). A missense point mutation at codon 111 (Tyr111His) was not associated with any obesity-related phenotypes. In conclusion, adiponectin DNA sequence variations might play a role in the complications of morbid obesity and should be further investigated.

Greater than predicted decrease in energy expenditure during exercise after body weight loss in obese men.

Abstract: This study was performed retrospectively to investigate whether exercise energy expenditure (EE) measured during a standardized treadmill protocol (4.5 km/h at 0% grade) falls below predicted values after body weight loss in obese men. A reference equation was established to predict net exercise EE in a control sample of 83 obese individuals (27 kg/m(2)< or = body mass index <45 kg/m(2)), using age, fat mass and fat-free mass as independent variables. This equation was then used to predict net exercise EE in another group of 11 obese men before and after a 15-week drug-based weight loss programme that was coupled with energy restriction [-2929 kJ/day (-700 kcal/day)]. Body weight and body composition were determined by hydrodensitometry. Net exercise EE, insulin, leptin, 3,3',5-tri-iodothyronine and free thyroxine were measured after an overnight fast at baseline and 2-4 weeks after the end of the programme, when subjects were weight stable. Body weight was significantly reduced (-11%; P <0.01) at the end of the weight loss programme. At baseline, measured net exercise EE was similar to that predicted from the regression equation [19.6 and 19.8 kJ/min (4.69 and 4.74 kcal/min) respectively; not significant]. However, after the end of the intervention, measured net exercise EE was significantly below the predicted value [15.5 and 17.3 kJ/min (3.71 and 4.14 kcal/min) respectively; P <0.01]. The difference between the predicted and the measured fall in net exercise EE was significantly associated with changes in leptin concentration ( r =0.79, P <0.01), even after correction for changes in fat mass and insulin. These observations suggest that net exercise EE falls below predicted values after body weight loss. In addition, this greater than predicted decrease in net exercise EE was associated with changes in leptin.

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

Abstract: 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 powe...

Genome-wide linkage scan for physical activity levels in the Quebec Family study.

Abstract: SIMONEN, R. L., T. RANKINEN, L. PERUSSE, T. RICE, D. C. RAO, Y. CHAGNON, and C. BOUCHARD. Genome-Wide Linkage Scan for Physical Activity Levels in the Quebec Family Study. Med. Sci. Sports Exerc., Vol. 35, No. 8, pp. 1355–1359, 2003.Purpose and MethodsIt is commonly recognized that there is

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

Abstract: 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.

Effect of malnutrition during the first year of life on adult plasma insulin and glucose tolerance

Abstract: There is evidence linking intrauterine growth retardation with increased cardiovascular risk and diabetes mellitus (DM) later in life. However, little is known about the association between malnutrition during the first year of life and metabolic abnormalities in adulthood. The objective of this study was to assess the effect of documented malnutrition during the first year of life on glucose tolerance, plasma insulin, lipid profile, and blood pressure in early adulthood, as well as to assess the interaction between body mass index (BMI) and malnutrition on these variables. A study group of young men with a documented history of malnutrition during their first year of life was recruited from 4 pediatric hospitals in Mexico City and compared with a control group. Subjects included were 52 men, aged 20.2 +/- 3.6 years, with a mean birth weight of 3.0 +/- 0.7 kg and documented malnutrition in their first year of life; controls were 50 men, aged 23.3 +/- 1.8 years, with a mean birth weight of 3.2 +/- 0.5 kg. Insulin and glucose concentrations, fasting and in response to an oral glucose load, plasma lipids, blood pressure, and an insulin sensitivity index (ISI) were measured. The areas under the curves of glucose (AUCG) and insulin (AUCI) were significantly higher in cases (P =.012 and <.002, respectively), independent of birth weight, BMI, or age. BMI was significantly associated with fasting plasma insulin (FPI), AUCI, ISI, triglyceride, and high-density lipoprotein (HDL)-cholesterol concentrations in cases, but not in controls. These data suggest that early malnutrition in extrauterine life, independently of birth weight, has an adverse effect on insulin metabolism and glucose tolerance in young men, and it worsens as body mass increases even within the normal range of BMI. Therefore, it is advisable to prevent obesity in individuals exposed to early malnutrition.

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

Abstract: SKINNER, J. S., S. E. GASKILL, T. RANKINEN, A. S. LEON, D. C. RAO, J. H. WILMORE, and C. BOUCHARD. Heart Rate versus %VO2max: Age, Sex, Race, Initial Fitness, and Training Response—HERITAGE. Med. Sci. Sports Exerc., Vol. 35, No. 11, pp. 1908–1913, 2003.PurposeIn the HERITAGE Family Study, h

Long-Term Adiposity Changes Are Related to a Glucocorticoid Receptor Polymorphism in Young Females

Abstract: Male and female preadolescents and adolescents who participated in phase 1 of the Quebec Family Study, and who were retested about 12 yr later, were recruited and subdivided on the basis of a genetic variant within the intron 2 of the glucocorticoid receptor (GRL IVS2-BclI). The increase in sc adiposity over the 12-yr follow-up period in the 4.5/2.3 genotype female subgroup was more than twice that observed in the 4.5/4.5 and the 2.3/2.3 genotype subgroups (P < 0.01). The statistical significance of this difference was essentially unchanged after adjusting for changes, over time, in percent dietary energy as fat, alcohol consumption, and participation in vigorous physical activity. In male subjects, the same trend was found, but it did not reach statistical significance. In conclusion, this study suggests that a significant interaction effect exists between variation in the glucocorticoid receptor gene and body fat gain in female subjects experiencing the transition between adolescence and adulthood. Furt...

Increased Abdominal Obesity, Insulin and Glucose Levels in Nondiabetic Subjects with a T29C Polymorphism of the Transforming Growth Factor-β1 Gene

Abstract: Background: In humans, a T→C transition at nucleotide 29 in the region encoding the signal peptide sequence of the transforming growth factor (TGF)-β1, which results in a

Aging per se does not influence glucose homeostasis: in vivo and in vitro evidence.

Abstract: OBJECTIVE - To assess the effect of age on glucose metabolism by examining 1) glucose metabolism in young and middle-aged subjects when total or regional adiposity is taken into account and 2) in vitro glucose transport in adipose tissue explants from young and middle-aged women paired for total and abdominal adiposity. RESEARCH DESIGN AND METHODS - Study 1: body composition, subcutaneous abdominal and visceral adipose tissue areas, and fasting and oral glucose-stimulated glucose and insulin were measured in 84 young and 81 middle-aged men and in 110 young and 91 middle-aged women. Study 2: glucose uptake in subcutaneous abdominal and visceral adipose tissue explants were measured in eight young and eight middle-aged women. RESULTS - Study 1: young and middle-aged men showed similar subcutaneous abdominal tissue area, whereas fat mass and visceral adipose tissue were greater in middle-aged than in young men (P < 0.01). Fat mass and subcutaneous and visceral adipose tissue areas were greater in middle-aged as compared with young women (P < 0.01). Fasting plasma glucose and the glucose response to an oral glucose tolerance test were significantly higher in middle-aged than in young men and women (P < 0.001). Statistical control for visceral adipose tissue area eliminated the difference seen in glucose response in men and women. Study 2: glucose transport in subcutaneous and omental adipose tissue did not differ between young and middle-aged women. CONCLUSIONS - 1) Visceral obesity, more than age per se, correlates with glucose intolerance in middle-aged subjects; 2) aging does not influence in vitro adipose tissue glucose uptake.

The Pro12Ala PPARgamma2 gene missense mutation is associated with obesity and insulin resistance in Swedish middle-aged men.

Abstract: Background A missense mutation in exon B of the adipocyte-specific isoform peroxisome proliferator-activated receptor-γ2 (PPARγ2) has recently been described, leading to the substitution of proline to alanine at codon 12, which causes a reduction in the transcriptional activity of PPARγ2. The Pro12Ala PPARγ2 polymorphism has been variably associated with obesity, insulin sensitivity, and dyslipidemia. Aims and methods In the present study, we addressed the hypothesis that the Pro12Ala variant is associated with obesity and estimates of insulin, glucose, and lipid metabolism as well as circulating hormones including salivary cortisol in 284 unrelated Swedish men born in 1944. The subjects were genotyped by using PCR amplification of exon B of the PPARγ2 gene followed by digestion with the restriction enzyme BstUI. Results Tests for differences between the PPARγ2 genotypes revealed that the PPARγ2 Ala homozygotes (n = 6) had higher body mass index (P = 0.022), abdominal sagittal diameter (P = 0.038), and nearly 3 times higher fasting insulin levels (P < 0.001) as well as higher HOMA insulin-resistance index (P = 0.011) compared to the PPARγ2 Pro homozygotes (n = 186). This association was independent of body mass and fat distribution. In addition, subjects with the Ala/Ala genotype had lower total cholesterol (P = 0.012) as well as a trend toward lower high- and low-density lipoprotein cholesterol (P = 0.071 and P = 0.095) compared to the other PPARγ2 genotypes. Conclusion In summary, these findings both confirm and expand the current notion that the PPARγ2 gene might play a role in the etiology of obesity and that genetic variability in PPARγ2 is associated with variations in body fat mass and insulin sensitivity. Copyright © 2003 John Wiley & Sons, Ltd.

Impact of abdominal visceral fat, growth hormone, fitness, and insulin on lipids and lipoproteins in older adults

Abstract: We examined the relationship between abdominal visceral fat (AVF) and plasma concentrations of lipids and lipoproteins in 19 females (F) (not on estrogen) and 31 males (M) over the age of 60 (age = 66.8 years). In addition, the effects of growth hormone (GH) release, fitness (V?O2 peak), insulin, and glucose concentrations (both fasting and in response to an oral glucose tolerance test) on lipids were examined. Subjects were categorized by low (L) and high (H) AVF (L 130 cm2), fat mass (FM) (above or below median value), and AVF corrected for fat mass. Factorial analysis of variance (ANOVA) showed that when subjects were divided by AVF and FM, similar results were observed with H > L (P H for HDL, HDL2, HDL3, apo A1, and LDL/apo-B LDL. Gender differences were also observed with F > M for Chol, LDL, HDL, and HDL2. When AVF was corrected for FM, these gender differences were still present. After correcting for FM, differences remained between H and L AVF groups for VLDL, TG, VLDL-TG, apo-B, apo-B LDL, apo-B VLDL, apoB/A1 (P < .05). Twenty-four hour integrated GH concentration (IGHC) was inversely related to VLDL, TG, VLDL TG, LDL TG, apoB, apoB VLDL, apoB LDL, Chol/HDL, LDL/HDL, and apoB/A1 in F, but not M (P < .05). V?O2 peak was directly related to Chol, LDL, HDL3, and apoB LDL with stronger relationships observed in F. Fasting insulin was related to lipids and lipoproteins in both men and women. These data suggest that, in older adults, elevated levels of AVF, FM, and AVF corrected for FM are associated with unfavorable lipid-lipoprotein profiles and extend similar findings reported in younger males and females with elevated AVF. These data also support previous findings indicating that AVF is a primary determinant of GH release.

Effects of β2-Adrenergic Receptor Gene Variants on Adiposity: The HERITAGE Family Study

Abstract: We investigated whether the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenergic receptor gene were associated with body-fat and fat-distribution phenotypes measured before and in response to a 20-week endurance-training program. BMI, fat mass (FAT), percentage of body fat (%FAT), sum of eight skinfolds (SF8), and abdominal fat areas assessed by computed tomography were measured in adult sedentary white and black participants of the HERITAGE Family Study. Evidence of gene-by-obesity interaction was found in whites for several adiposity phenotypes measured before training. Analyses performed separately in nonobese and obese subjects revealed that obese men carrying the Glu27 allele have lower fat accumulation (BMI, FAT, and %FAT) than noncarriers. Among white obese women, Gly16Gly homozygotes had a lower fat accumulation (BMI, FAT, and SF8) than Arg16Gly and Arg16Arg carriers. In response to endurance training, white women with the Arg16Arg genotype exhibited a greater reduction in BMI, FAT, and %FAT. Results observed in blacks were mostly negative. These results suggest that polymorphisms in the beta2-adrenergic receptor gene influence the amount of body fat in white obese men (Gln27Glu) and women (Arg16Gly), as well as the changes in adiposity in response to endurance training in white women (Arg16Gly).

The Genetics of Human Obesity

Abstract: This chapter summarizes the research on the role of genetic variation in human obesity. It provides a brief review of our current understanding of the level of heritability and of the familial risk for increasing levels of excess body weight. Single-gene defects known to cause obesity are discussed. The results of a large number of association studies performed with candidate genes are described. The candidate genes with at least five positive studies are highlighted. All published genomic scan studies relevant to obesity are reviewed, with an emphasis on the linkage results characterized by apparent convergence in at least two cohorts. Finally, the role of gene–environment interactions in the response to chronic positive or negative energy balance is examined. Keywords: candidate genes; energy balance; gene–environment interactions; genetics; genomic scan; molecular markers; obesity; quantitative trait locus

Evidence for a Major Quantitative Trait Locus on Chromosome 17q21 Affecting Low-Density Lipoprotein Peak Particle Diameter

Abstract: Background— Several lines of evidence suggest that small dense LDL particles are associated with the risk of coronary heart disease. Heritability and segregation studies suggest that LDL particle size is characterized by a large genetic contribution and the presence of a putative major genetic locus. However, association and linkage analyses have thus far been inconclusive in identifying the underlying gene(s). Methods and Results— An autosomal genome-wide scan for LDL peak particle diameter (LDL-PPD) was performed in the Quebec Family Study. A total of 442 markers were genotyped, with an average intermarker distance of 7.2 cM. LDL-PPD was measured by gradient gel electrophoresis in 681 subjects from 236 nuclear families. Linkage was tested by both sib-pair–based and variance components–based linkage methods. The strongest evidence of linkage was found on chromosome 17q21.33 at marker D17S1301, with an LOD score of 6.76 by the variance-components method for the phenotype adjusted for age, body mass index...

A quantitative trait locus on 7q31 for the changes in plasma insulin in response to exercise training: the HERITAGE Family Study.

Abstract: Several genome-wide linkage scans have been carried out to identify quantitative trait loci for type 2 diabetes and related metabolic phenotypes. However, no previous linkage scans have focused on the response to exercise training of relevant metabolic traits. We performed a genome-wide linkage scan for baseline fasting glucose, insulin, and C-peptide and their responses to a 20-week exercise training program in nondiabetic white and black men and women from the HERITAGE Family Study. In SIBPAL linkage analyses, the maximum number of sibpairs available was 344 and 93 for baseline phenotypes and 300 and 72 for exercise training response phenotypes in whites and blacks, respectively. A total of 509 markers with an average spacing of 6.0 Mb were used. The strongest linkage was found for the changes in fasting insulin in response to exercise training with a marker in the leptin gene on 7q31 (empirical multipoint P = 0.0004) in whites. In blacks, the strongest linkage was observed for baseline fasting glucose on 12q13-q14 (empirical multipoint P = 0.0006). These regions harbor several potential candidate genes. The present findings may be important in identifying individuals at increased risk of developing type 2 diabetes and who are most likely to benefit from a physically active lifestyle.

Familial resemblance for muscle phenotypes in the HERITAGE family study

Abstract: RICO-SANZ, J., T. RANKINEN, D. R. JOANISSE, A. S. LEON, J. S. SKINNER, J. H. WILMORE, D. C. RAO, and C. BOUCHARD. Familial Resemblance for Muscle Phenotypes in the HERITAGE Family Study. Med. Sci. Sports Exerc., Vol. 35, No. 8, pp. 1360–1366, 2003.Introduction/PurposeWe hypothesized that ske

The agouti-related protein and body fatness in humans

Abstract: 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.