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Biomedical subjects

C Bouchard

Publications and source records attributed to C Bouchard.

At least 127 records · Page 7Linked to original sources
PubMed2001

The genetics of human obesity: recent progress.

The risk of becoming obese is higher in some families than in others. The risk (the lambda coefficient) is two to three fold for moderate obesity, but up to five to eight fold for severe obesity. Several genes exhibit mutations that can cause early onset severe obesity. These mutations are rare and account for only a small fraction of the cases of obesity. At this time, more than fifty genes have been shown in various studies to influence the energy balance, nutrient partitioning, or the age of onset of obesity. The results of these studies are generally disappointing and often contradictory. One approach is to scan the genome with a high number of polymorphic markers to identify chromosomal regions harboring genes implicated in the development of obesity. Such studies can be helpful in defining new targets to explore.

Family↗
PubMed2000

Human genomics and obesity: finding appropriate drug targets.

The increasing prevalence of obesity worldwide has prompted the World Health Organization (WHO) to classify it as a global epidemic. Around the globe, more than a half billion people are overweight, and the chronic disease of obesity represents a major threat to health care systems in developed and developing countries. The major health hazards associated with obesity are the risks of developing diabetes, cardiovascular disease, stroke, osteoarthritis and some forms of cancer. In this paper, we review the prevalence of obesity and its cost to health care systems and present the relative contribution of environmental conditions and genetic makeup to the development of obesity in people. We also discuss the concept of "essential" obesity in an "obesigenic" environment. Though weight gain results from a sustained imbalance between energy intake and energy expenditure, it is only recently that studies have identified important new mechanisms involved in the regulation of body weight. The etiology of the disease is presented as a feedback model in which afferent signals inform the central controllers in the brain as to the state of the external and internal environment and elicit responses related to the regulation of food intake and energy metabolism. Pharmaceutical agents may intervene at different levels of this feedback model, i.e., reinforce the afferent signals from the periphery, target the central pathways involved in the regulation of food intake and energy expenditure, and increase peripheral energy expenditure and fat oxidation directly. Since obesity results from genetic predisposition, combined with the proactive environmental situation, we discuss new potential targets for generation of drugs that may assist people in gaining control over appetite as well as increasing total energy expenditure and fat oxidation.

Animals↗
PubMed2000

Genome-wide linkage analysis of systolic and diastolic blood pressure: the Québec Family Study.

BACKGROUND: Blood pressure (BP), an important risk factor for coronary heart disease, is a complex trait with multiple genetic etiologies. While some loci affecting BP variation are known (eg, angiotensinogen), there are likely to be novel signals that can be detected with a genome scan approach. METHODS AND RESULTS: A genome-wide scan was performed in 125 random and 81 obese families participating in the Québec Family Study. A multipoint variance-components linkage analysis of 420 markers (353 microsatellites and 67 restriction fragment length polymorphisms) revealed several signals (P:<0.0023) for systolic BP on 1p (D1S551, ATP1A1), 2p (D2S1790, D2S2972), 5p (D5S1986), 7q (D7S530), 8q (CRH), and 19p (D19S247). Suggestive evidence (0.0023<P:<0.01) was found on 3q, 10p, 12p, 14q, and 22q. The results were encouraging for HSD3B1 (P:<0.03), AGT (P:<0.03), ACE (P:<0.02), and adipsin (P:<0.005) but null with regard to other candidates (eg, renin, and glucocorticoid and adrenergic receptors). CONCLUSIONS: Multiple linkage regions support the notion that risk for hypertension is due to multiple (ie, oligogenic) susceptibility loci. Comparisons across the complete, random, and obese samples suggest that some regions are specific to BP and others may involve obesity (eg, pleiotropy, epistasis, or gene-environment interaction). Some of these areas harbor known candidates. Others involve novel regions, some of which replicate previous reports and provide a focus for future studies to identify novel genes that influence interindividual variation in BP.

Age Distribution↗
PubMed2000

Relationship between lipid peroxidation and plasma fibrinogen in middle-aged men.

The relationship between lipid peroxidation (plasma malondialdehyde [MDA] concentration) and plasma fibrinogen level was analyzed in 144 men, aged 53-62 years. MDA was measured colorimetrically and fibrinogen with the thrombin method. Mean plasma MDA concentration was 12.6 (SD 1.2) micromol/L, plasma fibrinogen level 2.91 (0.47) g/L, and body mass index 27.1 (3.5) kg/m(2). Prevalence of smoking was 17%. MDA correlated moderately with fibrinogen. Both MDA and fibrinogen correlated positively with waist hip ratio (WHR) and blood leukocyte count, but inversely with VO(2)max. Both MDA and fibrinogen levels were higher in smokers than in non-smokers (p<0. 01). In multiple stepwise regression analysis, plasma MDA, VO(2)max, smoking, and leukocyte count explained 38.1% of the variance in plasma fibrinogen level, with the individual contributions reaching 20.6%, 9.7%, 5.5%, and 2.3%, respectively. WHR, serum triglycerides, and age did not enter the model. These data suggest that increased lipid peroxidation is associated with elevated plasma fibrinogen level in middle-aged men.

Arteriosclerosis↗
PubMed2000

A common polymorphism in the human insulin-like growth factor binding protein 3 gene.

A common polymorphism generated by an A to C transition at nucleotide 7580 in the third intron of the insulin-like growth factor binding protein 3 gene was found. This polymorphism can be identified by Nde 1 restriction of genomic DNA amplified with a specifically designed restriction enzyme site-generating oligonucleotide primer. The frequency of the A and C alleles was estimated at 0.6 and 0.4 in the Caucasians, 0.63 and 0.37 in Blacks, respectively.

Amino Acid Substitution↗
PubMed2000

7-year stability of blood pressure in the Canadian population.

BACKGROUND: The purpose of the study was to examine the 7-year stability of systolic (SBP) and diastolic (DBP) blood pressures in the Canadian population. METHODS: The sample included 1,503 participants 7-69 years of age from the 1981 Canada Fitness Survey who were remeasured in Campbell's Survey of 1988. Both SBP and DBP were adjusted for the effects of body mass index (BMI) using regression procedures. RESULTS: Interage correlations from baseline to follow-up ranged from -0.17 to 0.61 for SBP and from -0.22 to 0. 51 for DBP. With few exceptions, correlations were positive and significant, and were highest and most consistent in adulthood. Further, between 27 and 39% of participants in the upper or lower quintiles in 1981 remained there in 1988. There were few differences in adiposity between those who remained in the upper or lower quintiles and those who did not. One exception was that males who remained in the upper quintile of SBP had greater values for BMI, sum of skinfolds, and waist circumference at baseline. Among adults, the best predictor of future blood pressure was baseline blood pressure, which accounted for between 12 and 34% of the variance in follow-up blood pressure, followed by age, follow-up BMI, and, in females, baseline physical activity levels. CONCLUSIONS: Blood pressure demonstrated low to moderate stability over 7 years in Canada, and baseline level of adiposity was related to the stability of SBP in males.

Adolescent↗
PubMed2000

Cardiac dimensions, physical activity, and submaximal working capacity in youth of the Québec Family Study.

The relationships between cardiac dimensions and physical activity and submaximal working capacity were examined in 198 boys and 154 girls, aged 9-18 years, who were participants in the first phase of the Québec Family Study. The sample was divided into three age groups, 9-12 years, 13-15 years, and 16-18 years. Indicators of physical activity included estimated daily energy expenditure (EE) and time spent in moderate-to-vigorous physical activity (median metabolic equivalents of energy expenditure above resting metabolic rate >/=4.8). Submaximal physical working capacity (PWC(150)) was determined using a submaximal exercise test on a Monark cycle ergometer. Echocardiographically determined dimensions included posterior wall thickness, septal wall thickness, and left ventricular mass (LVM). The analyses were based on partial correlation and analysis of covariance, controlling for age and body surface area. Relationships between EE/physical activity variables and cardiac dimensions were low and, at best, moderate (r < 0.45). With subjects grouped into tertiles by indicators of physical activity, LVM was significantly different only among 16- to 18-year-old girls (157 g vs 134 g in the highest and lowest quartiles, respectively; P < 0.05). Correlations between cardiac dimensions and PWC(150) were also low (r < 0.30), with few significant relationships. In general, cardiac dimensions were not related to habitual physical activity and PWC(150) in young subjects aged 9-18 years. However, significant correlations were positive, as expected. LVM may be related to submaximal power output in boys since it accounts for 3% of the variance, after adjusting for age and BSA.

Adolescent↗
PubMed2000

Time course of oxidative stress after major burns.

OBJECTIVE: To evaluate oxidative stress resulting from major burns in humans. DESIGN: Prospective clinical study with control group. SETTING: Mechanically ventilated adult patients admitted with more than 30% total burn surface area. PATIENTS AND PARTICIPANTS: 20 patients with a mean body surface burned area of 54%. MEASUREMENTS AND RESULTS: The oxidative stress evaluation was based on measurements of trace elements, vitamins, antioxidant enzymatic activity and end-products of lipid peroxidation. During the first 5 days after injury burn patients exhibit a decrease in selenium and antioxidant vitamins (C, beta-carotene, lycopene) and an increase in lipid peroxidation products (TBARS). CONCLUSION: Our results suggest that major burn is associated with oxidative stress during the 5 days after the initial injury, as demonstrated by a simultaneous decrease in antioxidant vitamins and a large increase in TBARS.

Adult↗
PubMed2000

Determinants of bone mineral density in middle aged men: a population-based study.

Osteoporosis is a growing health problem not only in women but also in men. To assess determinants of bone mineral density (BMD) at the spine and proximal femur, a randomly selected sample of 140 Finnish men aged 54-63 years was measured using fan beam dual-energy X-ray absorptiometry. Isometric muscle strength was measured using a computerized measurement system and cardiorespiratory fitness was assessed with maximal oxygen uptake (VO2 max) using breath-by-breath respiratory gas analyses during an incremental bicycle ergometer exercise. Intakes of calcium and energy were estimated using 4-day food records. Smoking habits and alcohol consumption were assessed from an interview and a 4 week diary, respectively. Isometric muscle strength of triceps and biceps brachii, extensors and flexors of thigh and rectus abdominis correlated significantly with BMD (r = 0.18-0.35, p = 0.02-0.000). Calcium intake correlated positively with femoral (r = 0.19-0.28, p = 0.03-0.003), but not with lumbar BMD. In addition, calcium intake adjusted for dietary energy content (mg/MJ) correlated with femoral BMD (r = 0.25-0.36, p = 0.03-0.000). Smoking had no effect on BMD, whereas alcohol intake correlated positively with BMD at L2-L4 (r=0.19, p = 0.031). In the multiple linear regression analysis adjusted calcium intake predicted BMD in every site measured, while strength of abdominal muscles predicted BMD at Ward's triangle and femoral neck. Body weight was a predictor of trochanteric BMD. Body height was the best predictor of lumbar and femoral neck area. We conclude that low dietary calcium intake, weak muscle strength and low body weight are risk factors for low BMD in men.

Absorptiometry, Photon↗
PubMed2000

Functional and dysfunctional perfectionists: are they different on compulsive-like behaviors?

Both perfectionism and excessive responsibility have been linked to obsessive compulsive disorder (OCD). Up to now however, a greater number of studies have focused on the role of responsibility. The present study compared compulsive-like behavior of people with different styles of perfectionism. Sixteen functional perfectionists (FP) and 16 dysfunctional perfectionists (DP) were compared on three different tasks in order to explore OC type behavior such as doubting, checking and intrusions. Results show that DP participants, compared to FP participants, scored higher on an OC behavior scale, took significantly more time to complete a precision task and precipitated their decision when confronted with ambiguity. The two groups also tended to differ in their intrusive thoughts following an unsolved problem; FP participants were more preoccupied about solving the problem than about the quality of their performance, contrary to DP subjects. Results are discussed according to theoretical models of OCD.

Adult↗
PubMed2000

The small, dense LDL phenotype as a correlate of postprandial lipemia in men.

The atherogenic dyslipidemia of the insulin resistance syndrome is characterized by hypertriglyceridemia (hyperTG), elevated apolipoprotein (apo) B levels, reduced high-density lipoprotein (HDL) cholesterol concentrations and by an increased proportion of small, dense low-density lipoprotein (LDL) particles. Although the hyperTG-low HDL cholesterol dyslipidemia has been associated with an impaired clearance of dietary fat, the contribution of the small, dense LDL phenotype as an independent predictor of postprandial triglyceride (TG) clearance remains uncertain. We have therefore compared the postprandial TG response among three subgroups of men characterized by small, intermediate or large LDL particles in a total sample of 69 men (mean age +/- SD; 45.1 +/- 10.5 years). To identify men with small versus large LDL particles, the first (LDL peak particle diameter < 251.9 A) and the third (> 257.6 A) tertiles of the distribution of LDL particle diameters were used as cutoff points. Men with small, dense LDL particles had the expected fasting dyslipidemic profile (high TG-low HDL cholesterol levels) compared to men with large, buoyant LDL particles. The oral lipid tolerance test revealed that men with small, dense LDL particles had significantly higher total-, large-, and medium-TG-rich lipoprotein (TRL) responses to a fatty meal than men with large LDL particles (P < 0.03). In addition, within a subgroup of normolipidemic men (TG < 2.3 mmol/l and HDL cholesterol > 0.9 mmol/l), those with small, dense LDL particles had higher levels of total-, medium- and small-TRL responses compared to men with large, buoyant LDL particles (P < 0.05). Moreover, normotriglyceridemic men with small, dense LDL had higher levels of small-TRLs measured 8 h after the ingestion of the fat meal (P < 0.05) compared to normolipidemic men with large, buoyant LDL particles. Results of the present study suggest that the dense LDL phenotype may be an additional fasting marker of an exaggerated postprandial TG response and of an impaired clearance of TRLs.

Adult↗
PubMed2000

Linkage and association studies of the lipoprotein lipase gene with postheparin plasma lipase activities, body fat, and plasma lipid and lipoprotein concentrations: the HERITAGE Family Study.

Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglyceride (TG)-rich lipoproteins. The aims of the present study were (1) to test for potential linkages (sib-pair method) between postheparin plasma lipase (lipoprotein and hepatic lipase) activities, body fatness, plasma lipid concentrations, and LPL polymorphisms (Ser447Ter and a tetranucleotide repeat) and microsatellite markers flanking the LPL locus (D8S261 and D8S258); and (2) to investigate associations between the LPL Ser447Ter (S447X) polymorphism and these phenotypes. Data on 190 parents and 312 adult offspring from 99 Caucasian families participating in the HERITAGE Family Study were available for this study. Data were adjusted for the effects of age within sex, and lipases, lipid variables, and abdominal visceral fat were further adjusted for fat mass. A suggestive linkage was observed only between the S447X polymorphism and very-low-density (VLDL)-apolipoprotein B (apo B) (332 sib-pairs, P = .013). The S447X polymorphism was not associated with body fat phenotypes or postheparin plasma LPL (PH-LPL) activity (men, P = .19; women, P = .47). In contrast, the X447 allele carriers had lower plasma TG (men and women, P = .01), VLDL-TG (men and women, P = .01), and VLDL-apo B (men and women, P = .009). The relationships between the X447 allele and plasma TG, VLDL-TG, and VLDL-apo B in both genders were observed in obese (body mass index [BMI] > or = 30 kg/m2) but not in normal-weight (BMI < 25 kg/m2) subjects. Thus, the S447X polymorphism of the LPL gene is not associated with body fatness and postheparin plasma lipase activities. However, the obese carriers of the X447 allele have plasma TG, VLDL-TG, and plasma cholesterol/high-density lipoprotein cholesterol (HDL-C) levels equivalent to those of normal-weight sedentary adults.

Adipose Tissue↗
PubMed2000

Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study.

We studied the effects of 20 weeks of supervised cycle-ergometer exercise on plasma lipids in 675 healthy, sedentary, normolipidemic white and black men and women aged 17 to 65 years, participating in the HERITAGE Family Study. Fasting plasma lipids were assessed twice at baseline and 24 and 72 hours after the last exercise session and adjusted for plasma volume changes. No significant differences from the mean baseline levels were observed for total, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B (Apo B). A significant reduction (P < .01) from baseline levels in plasma total and VLDL triglycerides was observed only in the 24-hour posttraining specimens, reflecting a response to the last bout of exercise. High-density lipoprotein (HDL) cholesterol increased 3.6% for the combined group, primarily due to an increase in HDL2, with an associated increase in Apo A-1 (P < .001). No significant differences were noted in the HDL response by sex, race, or age. An inverse correlation (r = -.241) was observed between the increase in HDL cholesterol and change in body fat only in men, and the increase in HDL cholesterol was unrelated to the change in maximal oxygen uptake (VO2max).

Adolescent↗
PubMed2000

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

Adult↗
PubMed2000

Genome-wide search for genes related to the fat-free body mass in the Québec family study.

Fat-free mass (FFM) consists mostly of skeletal muscle and bone tissues, and identification of the genes and molecular mechanisms involved in the control of FFM would have implications for the understanding of sarcopenia and potentially osteoporesis associated with aging, as well as the response to starvation, refeeding, anorexia, and any other conditions in which lean body mass is important. A genome-wide search for genes related to body leanness has been completed in the Quebec Family Study (QFS). Microsatellite markers (N = 292) from the 22 autosomal chromosomes were typed. The mean spacing of the markers was 11.9 centimorgans (cM) (range, <0.1 to 41). FFM was calculated from percent body fat, derived from underwater weighing, and body weight and was adjusted by regression for age and sex effects before analysis. A maximum of 336 sib pairs or 609 pairs of extended relatives were analyzed using single-point Haseman-Elston regression (SIBPAL and RELPAL) and multipoint variance component (SEGPATH) linkage analyses. Significant linkages were observed on chromosomes 15q25-q26 for a CA repeat within the insulin-like growth factor 1 receptor (IGF1R) gene (Lod score = 3.56) and at 18q12 with D18S877 (Lod score = 3.53) and D18S535 (Lod score = 3.58), 2 markers located 10 cM apart. A moderately significant linkage was also observed on chromosome 7p15.3 with the marker D7S1808 (Lod score = 2.72). The most obvious candidate genes within the regions identified by these linkages include the IGF1R on 15q and neuropeptide Y (NPY) and growth hormone-releasing hormone (GHRH) receptor on 7p. On 18q, the melanocortin receptor 4 (MC4R) is not likely the candidate gene for the observed linkage. This study represents the first genome-wide search for genes that may be involved in the regulation of the lean component of body mass in humans.

Adult↗
PubMed2000

Human papillomaviruses and vulvar vestibulitis.

OBJECTIVE: To assess the relationship between human papillomavirus (HPV) infection and vulvar vestibulitis syndrome. METHODS: From November 1995 to December 1997, 135 women with vulvar vestibulitis were compared with 322 controls who had no evidence of vulvar vestibulitis. Human papillomavirus DNA was amplified by polymerase chain reaction and detected with liquid-capture molecular assay. RESULTS: Human papillomavirus DNA was found in 29.6% of cases and in 23.9% of controls (relative risk [RR] 1.4; 95% confidence interval [CI].8, 2.2). The prevalence of HPV tended to decrease with increasing duration of pain among cases. Thus, prevalences were 37. 5%, 29.6%, and 22.0% for pain durations of 3-6 months, 7-12 months, and 13-24 months, respectively (P =.14). Prevalence of HPV also tended to increase with pain intensity among cases, but that association was not statistically significant (P =.57). Prevalence percentages for women with low, moderate, or severe pain were 27.5%, 28.8%, and 34.4%, respectively. Prevalence of HPV was slightly higher in cases with the most severe pain (34.4%) than in controls (23.9%) (RR 1.8; 95% CI.8, 4.0). In cases with the most pain in the shortest time (3-6 months), prevalence of HPV was double that of controls (50% versus 23.9%) (RR 3.5; 95% CI 1.0, 12.7; P =.054). CONCLUSION: There was little support for the idea that HPV might be related to vulvar vestibulitis.

Adult↗
PubMed2000

Complex segregation analysis of blood pressure and heart rate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Complex segregation analysis of baseline resting blood pressure (BP) and heart rate (HR) and their responses to training (post-training minus baseline) were performed in a sample of 482 individuals from 99 white families who participated in the HERITAGE Family Study. Resting BP and HR were measured at baseline and after a 20-week training program. Baseline resting BP and HR were age-adjusted and age-BMI-adjusted, and the responses to training were age-adjusted and age-baseline-adjusted, within four gender-by-generation groups. This study also analyzed the responses to training in two subsets of families: (1) the so-called "high" subsample, 45 families (216 individuals) with at least one member whose baseline resting BP is in the high end of the normal BP range (the upper 95th percentile: systolic BP [SBP] > or = 135 or diastolic BP [DBP] > or = 80 mm Hg); and (2) the so-called "nonhigh" subsample, the 54 remaining families (266 individuals). Baseline resting SBP was influenced by a multifactorial component (23%), which was independent of body mass index (BMI). Baseline resting DBP was influenced by a putative recessive locus, which accounted for 31% of the variance. In addition to the major gene effect, which may impact BMI as well, baseline resting DBP was also influenced by a multifactorial component (29%). Baseline resting HR was influenced by a putative dominant locus independent of BMI, which accounted for 31% of the variance. For the responses to training, no familiality was found in the whole sample or in the nonhigh subsample. However, in the high subsample, resting SBP response to training was influenced by a putative recessive locus, which accounted for 44% of the variance. No familiality was found for resting DBP response to training. Resting HR response to training was influenced by a major effect (accounting for 35% of the variance), with an ambiguous transmission from parents to offspring.

Adolescent↗