Showing papers by "Claude Bouchard published in 2007"
TL;DR: Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
Abstract: Background Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. Methods The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). Results The average weight change in control subjects was less than ±2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastropl...
4,297 citations
TL;DR: Cross‐sectional associations between short sleep duration and variations in body fat indices and leptin levels during adulthood during adulthood are explored in a sample of men and women involved in the Québec Family Study.
Abstract: CHAPUT, JEAN-PHILIPPE, JEAN-PIERRE DESPRES, CLAUDE BOUCHARD, AND ANGELO TREMBLAY. Short sleep duration is associated with reduced leptin levels and increased adiposity: results from the Quebec Family Study. Obesity. 2007;15:253-261. Objective: To explore cross-sectional associations between short sleep duration and variations in body fat indices and leptin levels during adulthood in a sample of men and women involved in the Quebec Family Study. Research Methods and Procedures: Anthropometric mea- surements, plasma lipid-lipoprotein profile, plasma leptin concentrations, and total sleep duration were determined in a sample of 323 men and 417 women ages 21 to 64 years. Results: When compared with adults reporting 7 to 8 hours of sleep per day, the adjusted odds ratio for overweight/ obesity was 1.38 (95% confidence interval, 0.89 to 2.10) for those with 9 to 10 hours of sleep and 1.69 (95% confidence interval, 1.15 to 2.39) for those with 5 to 6 hours of sleep, after adjustment for age, sex, and physical activity level. In each sex, we observed lower adiposity indices in the 7- to 8-hour sleeping group than in the 5- to 6-hour sleeping group. However, all of these significant differences disap- peared after statistical adjustment for plasma leptin levels. Finally, the well-documented regression of plasma leptin levels over body fat mass was used to predict leptin levels of short-duration sleepers (5 and 6 hours of sleep), which were then compared with their measured values. As ex- pected, the measured leptin values were significantly lower than predicted values. Discussion: There may be optimal sleeping hours at which body weight regulation is facilitated. Indeed, short sleep duration predicts an increased risk of being overweight/ obese in adults and is related to a reduced circulating leptin level relative to what is predicted by fat mass. Because sleep duration is a potentially modifiable risk factor, these find- ings might have important clinical implications for the prevention and treatment of obesity.
467 citations
TL;DR: Evidence is provided that short- and long-duration sleep times are associated with type 2 diabetes/IGT in adults, even after adjustment for several confounders.
Abstract: Aims/hypothesis
The aim of this study was to assess the relationship between sleep duration and type 2 diabetes or impaired glucose tolerance (IGT).
201 citations
155 citations
TL;DR: This study underlines the importance of visceral AT accumulation in the previously reported association between CRF and metabolic complications predictive of coronary heart disease and type 2 diabetes mellitus.
Abstract: Background It has been suggested that overweight and obese individuals with an adequate level of cardiorespiratory fitness (CRF), the so-called fat and fit, are at reduced risk of coronary heart disease and type 2 diabetes mellitus. Methods To determine whether individuals with low CRF have more visceral adipose tissue (AT) accumulation compared with individuals with high CRF and to verify whether low CRF is associated with a poorer metabolic profile, we performed a cross-sectional study of 169 asymptomatic men without diabetes mellitus (mean ± SD body mass index [calculated as weight in kilograms divided by height in meters squared], 25.9 ± 4.4; and mean ± SD age, 37.1 ± 14.0 years). Abdominal AT accumulation, CRF, and indexes of plasma glucose-insulin homeostasis and of the lipoprotein-lipid profile were measured. Results More visceral AT accumulation was observed among men in the lowest tertile of CRF compared with men in the highest tertile of CRF (mean ± SD, 139.6 ± 70.2 cm 2 vs 74.7 ± 41.6 cm 2 ; P P P P = .002) than men with high CRF. After matching individuals with similar body mass index values but with high or low CRF, men with low CRF were characterized by more visceral AT accumulation than men with high CRF (mean ± SD, 114.4 ± 59.9 cm 2 vs 87.8 ± 49.1 cm 2 ; P Conclusion This study underlines the importance of visceral AT accumulation in the previously reported association between CRF and metabolic complications predictive of coronary heart disease and type 2 diabetes mellitus.
144 citations
TL;DR: It is not uncommon to read or hear in some quarters that biology has nothing to do with the current epidemic of excess weight, but there are biologists who hold the view that it is caused by vulnerabilities in the authors' genome.
Abstract: It is hard to dispute the fact that the prevalence of overweight and obesity is increasing around the world and that the obese are becoming more severely obese. However, there are few certainties concerning the true causes of the phenomenon. We often hear that as the human gene pool could not have changed rapidly enough to explain this acute rise in prevalence, the latter is undoubtedly caused by changes in our environment and our way of life. It is not uncommon to read or hear in some quarters that biology has nothing to do with the current epidemic of excess weight. But the converse is also true; there are biologists who hold the view that it is caused by vulnerabilities in our genome. As is generally the case when such diametrically opposed views are upheld, the truth lies somewhere in the middle.
135 citations
TL;DR: The evidence for the presence of familial aggregation for the individual components of MetS and their heritability levels is summarized and an overview of the studies that have dealt with candidate genes for MetS is provided.
Abstract: The concept of a metabolic syndrome (MetS), a cluster of pre-clinical metabolic alterations commonly associated with obesity, is the object of much debate. Genetic studies have the potential to contribute to some of the key questions, including the true nature of the cluster of pre-clinical features and whether it is associated with human genetic variation. This review summarizes the evidence for the presence of familial aggregation for the individual components of MetS and their heritability levels. It also provides an overview of the studies that have dealt with candidate genes for MetS. Potential leads from genome-wide linkage scans are also discussed. The assumption is made that obesity, ectopic fat deposition and abnormal adipose tissue metabolism are responsible for alterations in lipid metabolism, which in turn generates the commonly observed pre-clinical shifts in glucose tolerance, lipids and lipoprotein profile, blood pressure, inflammatory markers, endothelial function, and a prothrombotic state. Progress in the understanding of the genetic basis of MetS should occur as soon as a consensus is reached on the true nature of MetS, its components and diagnostic criteria.
118 citations
TL;DR: The rationale and design of the first study based on the ACLS genetics resource focusing on hypertension as the health outcome are introduced, and the associations of cardiorespiratory fitness and body mass index (BMI) with the risk of hypertension are reported.
Abstract: Introduction: Cardiorespiratory fitness and regular physical activity are inversely associated with the risk of hypertension, and exercise training has been shown to lower elevated blood pressure (BP). Genetic factors contribute significantly to the interindividual differences in endurance training-induced changes in BP. However, similar data on the genotype-by-fitness interactions on the risk of hypertension are scarce. Methods: In 2000, we started a systematic collection of blood samples from all consenting subjects of the Aerobics Center Longitudinal Study (ACLS) with a goal to generate a resource for studies addressing genotype-by-fitness interaction effects on various health-related end points. Here, we introduce the rationale and design of the first study based on the ACLS genetics resource focusing on hypertension as the health outcome (HYPGENE study), and we report the associations of cardiorespiratory fitness and body mass index (BMI) with the risk of hypertension. All HYPGENE subjects (N = 1234) were healthy and normotensive at their first clinic visit. Cases (N = 629) developed hypertension during the follow-up period (mean 8.7 yr), whereas controls (N = 605) remained normotensive (mean follow-up 10.1 yr). Results: Cardiorespiratory fitness was the strongest predictor of the hypertension risk, with each maximal metabolic equivalent unit being associated with a 19% lower risk (95% confidence interval [95% CI], 12-24%). Each baseline BMI unit was associated with a 9% higher hypertension risk (95% CI, 4-13%). However, the association of BMI was greatly attenuated (odds ratio 1.04 [95% CI, 0.99-1.09]) when fitness also was included in the model. Conclusions: The HYPGENE study will provide an excellent resource to address hypotheses regarding the genetic basis of hypertension while taking cardiorespiratory fitness level into account.
81 citations
TL;DR: Suggestible evidence is found that the Arg16Gly polymorphism in the gene encoding for the beta(2)-adrenergic receptor may associate with endurance performance status in white men.
Abstract: The Arg16Gly single nucleotide polymorphism of the human beta(2)-adrenoceptor (ADRB2) gene was evaluated in a case-control study that included 313 white male elite endurance athletes and 297 white male sedentary controls (SCs) recruited in a multicenter project from North America, Finland, and Germany. The groups were matched by country of origin. The elite endurance athletes were required to have a maximum oxygen uptake > or = 75 mL.kg(-1).min(-1) (mean [SD], 79.0 [3.5]), whereas SC subjects had to be sedentary with a measured maximum oxygen uptake < or = 50 mL.kg(-1).min(-1) (40.1 [7.0]). Polymerase chain reaction technique was used to amplify the single nucleotide polymorphism-containing region in codon 16 of the ADRB2 gene. ADRB2 genotypes were in Hardy-Weinberg equilibrium in both groups. Genotypes did not differ between countries or sports of the athletes. The chi(2) analysis for the genotype distribution showed a significant difference between the 2 cohorts (P = .030), suggesting a positive association between the tested Arg16Gly polymorphism and endurance performance. Comparing carriers vs non-carriers for the 2 alleles, an excess of Gly allele carriers was seen in the SC group (P = .009), indicating an unfavorable effect of the Gly allele with respect to the performance status. In conclusion, we found suggestive evidence that the Arg16Gly polymorphism in the gene encoding for the beta(2)-adrenergic receptor may associate with endurance performance status in white men.
63 citations
TL;DR: This study provides an illustrative example of how physical activity and fitness level modifies the associations between a candidate gene and outcome phenotype and expresses the expression of the genotype effect is modulated by physical activity or cardiorespiratory fitness level.
Abstract: Contributions of the DNA sequence variation at the endothelin 1 locus to the risk of hypertension and to endurance training-induced changes in blood pressure were investigated in the Aerobics Center Longitudinal Study and the Health, Risk Factors, Exercise Training and Genetics Family Study cohorts. We identified 586 normotensive control subjects and 607 incident hypertensive case subjects from the Aerobics Center Longitudinal Study cohort (all whites) who were normotensive and healthy at their first clinic visit. The case subjects were diagnosed with hypertension during an average follow-up of 9.5 years, whereas the control subjects remained normotensive. The allele and genotype frequencies of 5 endothelin 1 haplotype tagging single nucleotide polymorphisms did not differ significantly between the case and control subjects. However, we observed a significant (P0.0025) interaction between the endothelin 1 rs5370 (G/T; Lys198Asn) genotype and cardiorespiratory fitness level on the risk of hypertension: among low-fit subjects, the rs5370 minor allele (T; 198Asn) was associated with higher risk of hypertension (odds ratio: 1.95; 95% CI: 1.36 to 2.81; P0.0003), whereas the risk did not differ among genotypes in high-fit subjects. In the white Health, Risk Factors, Exercise Training and Genetics subjects (N480), the rs5370 T allele was associated with blunted systolic blood pressure (P0.0046) and pulse pressure (P0.0016) responses to a 20-week endurance training program. The Lys198Asn variant of the endothelin 1 locus is associated with blood pressure phenotypes in whites. However, the expression of the genotype effect is modulated by physical activity or cardiorespiratory fitness level. Our study provides an illustrative example of how physical activity and fitness level modifies the associations between a candidate gene and outcome phenotype. (Hypertension. 2007;50:1120-1125.)
61 citations
TL;DR: Previous findings that the ADIPOQ 45T-->G variant contributes to overall fatness and abdominal obesity are confirmed and variants in the promoter region of both ADIPOR genes contribute to substrate oxidation.
TL;DR: This work tested the hypothesis that peroxisome proliferator-activated receptor-δ (PPARδ) gene polymorphisms are associated with cardiorespiratory fitness and plasma lipid responses to endurance training.
Abstract: We tested the hypothesis that peroxisome proliferator-activated receptor-δ (PPARδ) gene polymorphisms are associated with cardiorespiratory fitness and plasma lipid responses to endurance training....
TL;DR: Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle.
Abstract: Objective: To examine the importance of lipin 1 (LPIN1) gene variation in energy and glucose metabolism. Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1 was identified as the mutated gene in the fatty liver dystrophy mouse, which exhibits lipin deficiency and features of human lipodystrophy.
Research Methods and Procedures: We genotyped five LPIN1 polymorphisms and tested for association with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and glucose concentration, and obesity-related phenotypes, including BMI, body fat percentage, sum of six skinfolds, and waist circumference in 712 subjects of the Quebec Family Study.
Results: The strongest results were generation-specific. In parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In offspring, carriers of the C allele of the IVS18 + 181C>T variant had significantly higher (p T variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of relationships.
Discussion: These findings support the hypothesis that sequence variation in the LPIN1 gene contributes to variation in RMR and obesity-related phenotypes potentially in an age-dependent manner.
TL;DR: The nature of the associations among physical activity level, fitness, and longevity, with special reference to the role of human genetic variation, is reviewed, and potential reasons for different outcomes of these large twin studies are discussed.
Abstract: The importance of regular physical activity to human health has been recognized for a long time, and a physically active lifestyle is now defined as a major component of public health policies. The independent contribution of regular physical activity to lower morbidity and mortality rates is generally accepted, and the biologic mechanisms mediating these health effects are actively investigated. A few years ago, data from the Finnish Twin Registry suggested that genetic selection may account for some of the physical-activity-related benefits on mortality rates. However, results from the Swedish Twin Registry study reported by Carlsson et al. in the current issue of the Journal (Am J Epidemiol 2007;166:255-259) do not support the genetic selection hypothesis. In this commentary, the authors review the nature of the associations among physical activity level, fitness, and longevity, with special reference to the role of human genetic variation, and discuss potential reasons for different outcomes of these large twin studies.
TL;DR: The contribution of three polymorphisms in the endothelial nitric oxide synthase (NOS3) gene to discriminate elite endurance athletes (EEA) from sedentary controls (SC) was examined in this paper.
Abstract: In the Genathlete study, we examined the contribution of three polymorphisms in the endothelial nitric oxide synthase (NOS3) gene to discriminate elite endurance athletes (EEA) from sedentary controls (SC). The EEA group included a total of 316 Caucasian males with a VO2max >75 mL/kg. The SC group comprised 299 unrelated sedentary Caucasian males who had VO2max values below 50 mL/kg. The polymerase chain reaction technique was used to amplify a microsatellite (CA)(n) repeat in intron 13, a 27 bp repeat in intron 4 and a third fragment in exon 7 containing the Glu298Asp SNP. No difference was found between the EEA and SC groups for the 27 bp repeat and the Glu298Asp polymorphism. Chi-square analysis of the overall allelic distribution of the (CA)(n) repeat revealed no significant difference between the two groups (P=0.135). However, comparing carriers and non-carriers for the most common (CA)(n) repeat alleles, we found significant differences between SC and EEA, with more EEA subjects carrying the 164 bp allele (P=0.007). In summary, we found suggestive evidence that the 164 bp allele of the (CA)(n) repeat in intron 13 is associated with EEA status and may account for some of the differences between EEA and SC.
TL;DR: This study identified chromosomal regions encoding genes predisposing to the metabolic syndrome using composite factors derived from maximum likelihood‐based factor analysis using genetic data obtained from the Quebec Family Study.
Abstract: The metabolic syndrome represents a cluster of cardiovascular risk factors co-occurring in the same individual. The aim of this study was to identify chromosomal regions encoding genes predisposing to the metabolic syndrome using composite factors derived from maximum likelihood-based factor analysis. Genetic data were obtained from the Quebec Family Study and included 707 subjects from 264 nuclear families. Factor analyses were performed on eight metabolic syndrome-related phenotypes including waist circumference; BMI; systolic and diastolic blood pressure; and plasma insulin, glucose, triglyceride, and high-density lipoprotein-cholesterol levels. Three factors were identified and interpreted as general metabolic syndrome, blood pressure, and blood lipids, respectively. The general metabolic syndrome factor had high factor loadings (>0.4) for all phenotypes and explained 42% of the total variance, and family membership accounted for 45.6% of the factor variance. A genome-wide linkage scan performed with this first factor revealed the existence of a quantitative trait locus on chromosome 15 (86 cM) with a logarithm of odds score of 3.15. Suggestive evidence of linkage (logarithm of odds > 1.75) was also observed on chromosomes 1p, 3p, 3q, 6q, 7p, 19q, and 21q. These quantitative trait loci may harbor genes contributing to the clustering of the metabolic syndrome-related phenotypes.
TL;DR: Assessment of gene‐diet interaction effects on cardiovascular disease (CVD) risk factors in the Quebec Family Study cohort found no significant effect on waist circumference or fasting glucose concentrations.
Abstract: Objective: The aim of this study was to assess gene-diet interaction effects on cardiovascular disease (CVD) risk factors (waist circumference, plasma triacylglycerol, high-density lipoprotein-cholesterol and fasting glucose concentrations, and diastolic and systolic blood pressure) in the Quebec Family Study cohort.
Design: Sixty-four polymorphisms from 45 candidate genes were studied in 645 subjects. Dietary fat intake was obtained from a 3-day weighted food record.
Results: We observed 18 significant interactions at a p value ≤ 0.01. Among them, the Pro12Ala polymorphism in peroxisome proliferator-activated receptor γ, alone or in interaction with fat intake, significantly modulated waist circumference (p = 0.0005 for both effects). Additionally, the apolipoprotein E genotype in interaction with fat intake was significantly associated with diastolic and systolic blood pressure (p = 0.01 and p = 0.001, respectively). The ghrelin Leu72Met polymorphism also interacted with dietary fat in its relation to waist circumference and triacylglycerol concentrations (p = 0.0004 and p = 0.005).
Discussion: These results suggest that several alleles at candidate genes interact with dietary fat intake to modulate well-known CVD risk factors. The identification of gene-diet interaction effects is likely to provide useful information concerning the etiology of CVD.
TL;DR: This study suggests that models including genetic information from several candidate gene polymorphisms can significantly contribute to the changes in adiposity over time, that different genes may act at different ages and that genetic information could be useful for the identification of individuals at high risk for gaining body fat over time.
Abstract: Several candidate genes have been associated with obesity, but very few studies have tested more than one gene simultaneously. In this study, 15 polymorphisms in 10 candidate genes of obesity were tested for association with changes in adiposity measured over a period of 6–10 years in a maximum of 332 adult subjects with a wide range of adiposity (17.5
TL;DR: The beneficial effects of endurance training on plasma HDL(3)-c and apoA1 levels are evident in white women homozygous for the -629A allele, and the CETP and APOE genotypes account for up to 9% of the variance in HDL-c phenotypes in the HERITAGE Family Study.
Abstract: Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of endurance training were investigated i...
TL;DR: In summary, significant associations between relatively common USF1 genetic variants and CVD risk factors were observed in French Canadians.
Abstract: Cardiovascular (CVD) risk factors are under the influence of environmental and genetic factors. Human upstream transcription factor 1 gene (USF1) encodes for a transcription factor, which modulates the expression of genes involved in lipid and carbohydrate metabolic pathways. The aim of this study was to test the hypothesis that USF1 gene variants are associated with CVD risk factors in the Quebec Family Study (QFS). USF1 has been sequenced in 20 QFS subjects with high plasma apolipoprotein B100 (APOB) levels (>1.14 g/l) and small, dense low-density lipoprotein (LDL) particles (> or =250.7 Angstroms and A, and exon 11 c.*187 C>T) as well as the c.-56 A>G polymorphism, were genotyped and analyzed in 760 subjects from QFS. Association studies showed that women with c.561-100 A/A and c.*187 T/T genotypes had more favorable adiposity indices (<0.04). In summary, significant associations between relatively common USF1 genetic variants and CVD risk factors were observed in French Canadians.
TL;DR: Fasting insulin and SI responses to exercise training were associated with DNA sequence variation in FHL1 inwhite men, and whether these associations exist only in white men remains to be investigated.
Abstract: Aims/hypothesis
The expression of the four and a half LIM domains 1 gene (FHL1) is increased in the muscle of individuals who show an improvement in insulin sensitivity index (SI) after 20 weeks of exercise training. The aim of the present study was to investigate associations between three FHL1 single nucleotide polymorphisms (SNPs) and variables derived from an IVGTT, both in the sedentary state and in response to exercise training, in participants in the HERITAGE Family Study.
TL;DR: The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in whites, on 10q25-26 for baseline HR60 in blacks, and on 18q21-22 for both baseline HR50 and DeltaHR60 in whites.
Abstract: The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-wk endurance training pro...
TL;DR: PCTP gene variants are associated with LDL-PPD, a small, dense LDL phenotype associated with an increased cardiovascular disease risk found on a genome-wide scan performed on 236 nuclear families of the Quebec Family Study.
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TL;DR: A joint effort by the National Institute on Aging at NIH and the Centers for Disease Control and Prevention will compensate in part for the termination of the human obesity gene map publication project and OGMDB, which covered much more than association studies and was well received by the scientific community.
Abstract: In 1996, we began publishing in Obesity Research a review of the status of the human obesity gene map (1). Since then, 10 updates of the map have been published, the latest in 2006 covering the literature available as of the end of October 2005 (2). In 1999, an electronic version of the map was made available on the website of the Donald B. Brown Chair on Obesity at Université Laval in Quebec City, Canada. Later, in 2002, the web-based version of the map was migrated to the Human Genomics Laboratory web site at the Pennington Biomedical Research Center in Baton Rouge, LA, where I had moved. While the print version of the map continued to be a factual summary of the material published at a particular point in time, the web-based version (Obesity Gene Map Database or OGMDB) was enriched considerably and provided extensive linkages to other relevant resources. The printed version in Obesity (previously, Obesity Research) was well received by the scientific community, as evidenced by its relatively high rate of citation over the last 10 years ( 750 citations by the end of 2006). Similarly, the OGMDB resource enjoyed 15,000 hits per month in the last few years, with thousands of regular visitors. Interestingly, the most assiduous users were from the pharmaceutical industry and from biotechnology companies. Developing the yearly update of the map became progressively a major burden. For instance, the last rendition published in Obesity in 2006 reached a total of 116 journal pages. It had become an effort of a magnitude that could not be sustained without the addition of human resources dedicated solely to the project. Despite our best efforts, funds could not be raised in a timely fashion to make it possible for us to continue publishing these yearly updates. Fortunately, a joint effort by the National Institute on Aging at NIH and the Centers for Disease Control and Prevention will compensate in part for the termination of the human obesity gene map publication project and OGMDB. Indeed, these two entities have launched and are maintaining a database of human genetic association studies. The database can be accessed at http://geneticassociationdb.nih. gov. Obesity is not the main focus of the database, but it is included, along with many other diseases and conditions. While the human obesity gene map covered much more than association studies (i.e., Mendelian syndromes, human and animal model single gene defects, genomic scans performed in human cohorts and in animal models, transgenic and knockout murine data, etc.), the new NIH-CDC database focuses on one of the most critical lines of evidence to consider in assessing the role of gene polymorphisms. So it seems like a good time to move on. The field should continue to be well served by the new resource. The map project was made possible through the dedication and hard work of several colleagues at Université Laval and at the Pennington Biomedical Research Center. Even though I will not be able to thank them all here, I would like to express my gratitude to the very early collaborators, Drs. Louis Perusse and Yvon C. Chagnon, as well as John Weisnagel and Tuomo Rankinen, who joined the team soon thereafter. Thanks are also due to Drs. Eric E. Snyder, George Argyropoulos, and Aamir Zuberi, who brought additional expertise to the team in the later years. We were well supported by Diane Drolet in the early phase at Université Laval and, subsequently, by Brandon M. Walts and Nina Laidlaw at the Pennington Biomedical Research Center. I am also grateful for the contribution of the Donald B. Brown Chair on Obesity in the first few years of the project and of several units of the Pennington Biomedical Research Center in more recent times. Finally, I would like to thank the Editors of Obesity (Drs. Xavier Pi-Sunyer and, later, Barbara Corkey) and the Managing Editor, Deborah K. Moskowitz, for their encouragement and strong support for the publication of the annual update of the human obesity gene map over the last 10 years.
TL;DR: The findings indicate that the BMI is an important determinant of LV structure and was highest in youth 13–15 years, whereas other correlations involving the BMI were rather constant across age groups.
Abstract: The relationship between adiposity and cardiac dimensions were considered in healthy 9- to 18-year-old boys (n=198) and girls (n=154). Indicators of adiposity included the body mass index (BMI), sum of skinfolds (SSF) and trunk-to-extremity ratio (TER). The following left ventricular (LV) dimensions were measured by echocardiography: internal diameter (LVIDd); posterior wall thickness (PWT) and intraventricular septal wall thickness. LV mass (LVM) was estimated. In boys, 11 of 45 correlations were significant. The magnitude of the correlations increased across age groups and most of the correlations were significant in the oldest age group. In girls, 18 of 45 correlations were significant, but there were inconsistent patterns in the magnitude of the correlations across age groups. Correlations between BMI and LVIDd and LVM were highest in youth 13–15 years, whereas other correlations involving the BMI were rather constant across age groups. Correlations involving SSF were significant only in 9–12 and 13–15 year olds. There were no significant correlations involving TER in female subjects. In the total sample of boys, only correlations between the BMI and LV parameters were significant (r=0.14–0.38), except for the relationship between SSF and PWT (r=0.21). The TER was weakly associated with LV parameters. In the total sample of girls, correlations for LV parameters were significant for both the BMI (r=0.20–0.43) and SSF (r=0.18–0.28; except for LVIDd). TER was not significantly related to LV parameters except LVIDd (r=0.16). The findings indicate that the BMI is an important determinant of LV structure.
TL;DR: Smoking negates the beneficial effect of exercise training on erythrocyte resistance to free radical-induced hemolysis and the findings suggest the presence of familial effects in the response to ex vivo oxidation.
Abstract: Oxidant stress and overproduction of reactive oxygen species (ROS) contribute to the development of cardiovascular disease Oxidative modifications of low-density lipoproteins (LDL) are thought to play an early and critical role in atherogenesis LDL oxidation can be reproduced in vitro, but results usually show a large interindividual variation not entirely explained by the environment Free radical-induced hemolysis is also proposed to reveal the overall antioxidant capacity The roles of genetic factors and exercise on the variability of both measures were investigated The study was conducted in 146 healthy individuals from 28 families participating in a 20-week exercise-training program In addition to important biological and environmental influences on variation, significant familial aggregation was detected in all oxidation measures Exercise did not significantly modify the LDL oxidation parameters, but significantly increased resistance was observed in the free radical-induced hemolysis, especia
TL;DR: A two‐step fine mapping of a 20‐megabase region around a quantitative trait locus previously reported on chromosome 15q26 for abdominal subcutaneous fat in an extended sample of 707 subjects from 202 families from the Quebec Family Study is undertaken.
Abstract: Objective: In the present study, we undertook a two-step fine mapping of a 20-megabase region around a quantitative trait locus previously reported on chromosome 15q26 for abdominal subcutaneous fat (ASF) in an extended sample of 707 subjects from 202 families from the Quebec Family Study.
Research Methods and Procedure: First, 19 microsatellites (in addition to the 7 markers initially available on 15q24-q26; total = 26) were genotyped and tested for linkage with abdominal total fat, abdominal visceral fat, and ASF assessed by computed tomography and with fat mass (FM) using variance component-based approach on age- and sex-adjusted phenotypes. Second, 16 single nucleotide polymorphisms (SNPs) were genotyped and tested for association using family-based association tests.
Results: After the fine mapping, the peak logarithm of odds ratio (LOD) score (marker D15S1004) increased from 2.79 to 3.26 for ASF and from 3.52 to 4.48 for FM, whereas for abdominal total fat, the peak linkage (marker D15S996) decreased from 2.22 to 1.53. No evidence of linkage was found for abdominal visceral fat. Overall, for genotyped SNPs, three variants located in the putative MCTP2 gene were significantly associated with FM and the three abdominal fat phenotypes (p ≤ 0.05). The major allele and genotype of rs1424695 were associated with higher adiposity values (p < 0.004). The same trend was found for the two other polymorphisms (p < 0.05). None of the other SNPs was associated with adiposity phenotypes. The linkage for FM became non-significant (LOD = 0.84) after adjustment for the MCTP2 polymorphisms, whereas the one for ASF remained unchanged.
Discussion: These results suggest that the MCTP2 gene, located on chromosome 15q26, influences adiposity. Other studies will be needed to investigate the function of the MCTP2 gene and its role in obesity.