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Biomedical subjects

C Bouchard

Publications and source records attributed to C Bouchard.

At least 307 records · Page 17Linked to original sources
PubMed1997

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

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

Biomarkers↗
PubMed1997

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

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

Aged↗
PubMed1997

Physical activity, fibrinogen plasma level and gene polymorphisms in postmenopausal women.

The relations between habitual physical activity (PA), fibrinogen gene polymorphisms and plasma fibrinogen were investigated in 191 postmenopausal women. Subjects who reported PA at least 4 times/week had lower fibrinogen level (3.19 g/l; 95% CI 3.10; 3.27) than women reporting PA 2-3 times/week (3.43 g/l; 3.29; 3.58) or sedentary subjects (3.64 g/l; 3.33; 3.94). There were no differences in plasma fibrinogen across the alpha-fibrinogen (RsaI, TaqI) or beta-fibrinogen (MnlI, BclI, HindIII) genotypes, the frequencies of which were in a Hardy-Weinberg equilibrium. An interaction between RsaI, which was in complete linkage disequilibrium with TaqI, and PA on plasma fibrinogen was observed, even after adjustments for BMI, smoking and medication (p = 0.024). Among women homozygous for the common RsaI allele, the physically most active had lower fibrinogen level (p <0.001) compared to the physically less active subjects. These results suggest that, in postmenopausal women, the relation between physical activity and plasma fibrinogen is modulated by genetic variation in the alpha-fibrinogen gene.

Aged↗
PubMed1997

Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study.

BACKGROUND: The agouti yellow mouse shows adult onset of moderate obesity and diabetes. A depressed basal lipolytic rate in adipocytes or a decreased adrenergic tone arising from antagonizing alpha-melanocyte-stimulating hormone (MSH) activation of melanocortin receptors (MCR) could be at the origin of the obesity phenotype. MATERIAL AND METHODS: MCR 4 and 5 (MC4R, MC5R) genes were studied in the Québec Family Study. Sequence variations were detected by Southern blot probing of restricted genomic DNA, and mRNA tissue expression was detected by RT-PCR. Subjects with a wide range of weight were used for single-point sib-pair linkage studies (maximum of 289 sibships from 124 nuclear families). Analysis of variance across genotypes in unrelated males (n = 143) and females (n = 156) was also undertaken. Body mass index (BMI), sum of six skin-folds (SF6), fat mass (FM), percent body fat (%FAT), respiratory quotient (RQ), resting metabolic rate (RMR), fasting glucose and insulin, and glucose and insulin area during an oral glucose tolerance test were analyzed. RESULTS: MC4R showed polymorphism with NcoI, and MC5R, with PstI and PvuII, with a heterozygosity of 0.38, 0.10, and 0.20, respectively. Linkages were observed between MC5R and BMI (p = 0.001), SF6 (p = 0.005), FM (p = 0.001), and RMR (p = 0.002), whereas associations were observed in females between MC5R and BMI (p = 0.003), and between MC4R and FM (p = 0.002) and %FAT (p = 0.004). After correction for multiple tests, these p values are lowered by one tenth. MC4R and MC5R mRNAs have been detected in brain, adipose tissue, and skeletal muscle. CONCLUSIONS: MC4R and MC5R exhibit evidence of linkage or association with obesity phenotypes, but this evidence is strongest for MC5R.

Adolescent↗
PubMed1997

Small, dense LDL particle concentration correlates with plasminogen activator inhibitor type-1 (PAI-1) activity.

The relation between LDL subfractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subfractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tertile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tertile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9% of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.

Analysis of Variance↗
PubMed1997

Familial resemblance for body composition measures: the HERITAGE Family Study.

A sex-specific familial correlation model was used to assess the heritable contributions to several measures of body composition in 86 sedentary white families participating in the HERITAGE Family Study. For this study, sedentary families were recruited, tested for a battery of measures, endurance exercise trained for 20 weeks, and remeasured. This sample is unique in that activity level was controlled for in these families at baseline measurement. In this report, three body composition variables measured at baseline were analyzed, two indexing adiposity (total subcutaneous fat based on eight skinfold measurements [SF8] and percent body fat measured by underwater weighing techniques [%BF]) and one assessing fat free mass ([FFM] derived from underwater weighing). The maximal heritabilities for SF8 (34%) and %BF (62%) were consistent with those reported in previous studies. There were no sex nor generation differences in the familial correlations, and the spouse correlation was significant, consistent with the hypothesis that the familial aggregation reflects genetic and familial environmental factors. However, the results for FFM were very different. The most parsimonious pattern of familial resemblance was consistent with mitochondrial inheritance (i.e., mother-offspring and sibling correlations were equal and were larger than those for spouse and father-offspring pairs). Under the mitochondrial hypothesis, 39% of the variance was accounted for by familial/genetic effects. However, under a nonmitochondrial hypothesis, which could not be ruled out, 65% of the FFM phenotypic variance was accounted for by familial/genetic factors. This high heritability level, as compared with results from previous studies, is consistent with the hypothesis that activity may constitute an important environmental determinant of FFM. These alternative hypotheses for FFM warrant further investigation using complex multilocus-multitrait segregation models, which allow for major genetic, polygenic, and environmental sources of variance, as well as interactions among them.

Adipose Tissue↗
PubMed1996

[Electric burns: epidemiological and therapeutic aspects].

OBJECTIVES: A retrospective study of patients with electrical burns was conducted to choose criteria for initial dispatching and establish a treatment protocol for out patient management. METHODS: The study included 67 patients injured by electrical current and admitted at Edouard Herriot Hospital Burns Unit between January 1st 1990 and January 1st 1993. RESULTS: Low-voltage currents (< 1000 Volts) responsible for serious and immediate cardio-vascular diseases occurred in domestic accidents, mostly with children. High-voltage current (> 1000 Volts) responsible for deep burn injuries occurred in accidents at work and mostly with adults. Twenty-two were outpatients and 45 were admitted at once. Two died on admission, 24 were hospitalized less than five days, 11 required repeated surgical treatments and a long stay at hospital, and 8 were severely burned and were admitted to the intensive-care unit. Two required continuous venovenous hemodialysis for three weeks. Morbidity of the last three groups was nil, morbidity remained high in term of functional and aesthetic after-effects. CONCLUSION: Information on prevention of electrical burns should be intensified.

Accidents, Occupational↗
PubMed1996

The Trp64Arg mutation of the beta3 adrenergic receptor gene has no effect on obesity phenotypes in the Québec Family Study and Swedish Obese Subjects cohorts.

The beta adrenergic system plays a key role in regulating energy balance through the stimulation of both thermogenesis and lipid mobilization in brown and white adipose tissues in human and various animal models. Recent studies have suggested that a missense Trp64Arg mutation in the beta3 adrenergic receptor (ADRB3) gene was involved in obesity and insulin resistance. We have investigated the effect of this mutation on obesity-related phenotypes in two cohorts: the Québec Family Study (QFS) and the Swedish Obese Subjects (SOS). In QFS, no association was found between this mutation and body mass index (BMI), body fat including abdominal visceral fat, resting metabolic rate, various diabetes and cardiovascular risk factors, and changes in body weight and body fat over a 12-yr period. With the exception of RMR (P = 0.04), no evidence of linkage was detected between the mutation and phenotypes of QFS based on sib-pair data. In SOS, the frequency of the Trp64Arg allele was not significantly different between nonobese and obese female subjects and no association was found between the mutation and body weight gain over time. These findings do not support the view that there is an association between the Trp64Arg mutation in the ADRB3 gene and obesity.

Adult↗
PubMed1996

[Hemodynamic profile and serum cytokines in crush syndrome. Analogy with severe burns].

A 71-year-old woman remained under the rubble of her house for 4 hours after an accidental gas explosion. She suffered from a crush syndrome associating fractures, minor skin burns (< 10% body surface area), inhalation lung injury and moderate hypothermia (34 degrees C). In addition to local signs of compression of the lower limbs, the patient presented with hypovolemic shock and developed acute renal failure on day 3. We describe here the variations in hemodynamic and oxymetric parameters and cytokine response during the first post-injury week. A vasoplegic state resulting from low systemic vascular resistances with progressively increasing cardiac index, oxygen delivery and oxygen consumption closely followed the brief hypovolemic shock. Tumor necrosis factor-alpha remained below normal levels while interleukin-6 increased markedly with a major peak on day 2, in parallel with the drop in systemic vascular resistances. Interleukin-6 is a mediator of impairment in cell membrane function and a vasoconstriction inhibitor. Isolated increased interleukin-6 has been previously reported in severely burned patients suggesting a pathophysiological and hemodynamic similarity between crush syndrome and burn injury.

Aged↗
PubMed1996

Genetics of obesity in humans: current issues.

During the last decade, we have begun to understand some of the reasons why people become obese as assessed by excess body mass for height or excess total body fat content. Obesity frequently aggregates in families. However, this familial resemblance is caused not only by genetic effects but also by lifestyle, and environmental and cultural factors. Thus the genetic heritability of the obesity phenotypes accounts for up to 50% of the age- and gender-adjusted phenotypic variances. These results have been confirmed by overfeeding and negative energy balance studies. The effects of single segregating genes can be detected only under the correct experimental conditions. Most scientists in the area believe that these genes can be identified and that the DNA mutations associated with human obesities will be uncovered. Indeed, association and linkage studies, quantitative trait loci and positional cloning research strategies, and transgenic mouse models are sufficiently promising to suggest that these aims can be achieved. A review of the evidence reported thus far reveals that there are already four loci with strong evidence of linkage with obesity phenotypes in humans.

Animals↗
PubMed1996

A major gene for resting metabolic rate unassociated with body composition: results from the Québec Family Study.

A major gene hypothesis for resting metabolic rate (RMR) was investigated using segregation analysis (POINTER) of data on families participating in Phase 2 of the Québec Family Study. Complete analyses were conducted on RMR adjusted for age, and also on RMR adjusted for age and other covariates, primarily fat mass (FM) and fat-free mass (FFM). Prior to adjustment for covariates, support for a major gene hypothesis was equivocal-i.e., there was evidence for either a major gene or a multifactorial component (i.e., polygenic and/or familial environment). The multifactorial model was preferred over the major gene model, although the latter did segregate according to Mendelian expectations. However, after the effects of FM and FFM were accounted for, a major gene effect was unambiguous and compelling. The putative locus accounted for 57% of the variance, affected 7% of the sample, and led to high values of RMR. The lack of a significant multifactorial effect suggested that the familial etiology of RMR adjusted for FM and FFM was likely to be entirely a function of the major locus. Comparing the RMR results from pre- and post-adjustment for FM and FFM suggests a plausible hypothesis. We know from earlier studies in this sample that there is a putative major gene for FM and a major non-Mendelian effect for FFM. The current study leads us to speculate that: (1) the gene(s) affecting body size and body composition also may have an effect on RMR, and further (2) removal of the effect of the major gene(s) for body size and composition allowed for detection of an additional major gene affecting only the RMR. Thus, RMR appears to be an oligogenic trait.

Adipose Tissue↗
PubMed1996

Current status of the human obesity gene map.

An overview of the status of the human obestiy gene map up to October 1995 is presented. The evidence is drawn from several lines of clinical and experimental research. First, 12 loci linked to Mendelian disorders exhibiting obesity as one clinical feature are reviewed. Second, six loci causing obesity in rodent models of the disease are considered. Third, eight chromosomal regions where quantitative trait loci, identified by crossbreeding experiments with informative strains of mice, are defined. Fourth, 10 candidate genes exhibiting a statistical association with BMI or body fat are introduced. Fifth, nine loci found to be linked to a relevant phenotype are listed and the four cases for which the evidence for linkage is strongest are emphasized. The latter are mapped to 2p25, 6p21.3, 7q33 and 20q12-13.11. Finally, the studies that have concluded that there was no association or linkage with a marker or gene are also reviewed. It is recommended that a system be developed by the obesity research community to ensure that an accurate and easily accessible computerized version of the human obesity gene map becomes available in the near future.

Animals↗
PubMed1996

Genetic pleiotropy for resting metabolic rate with fat-free mass and fat mass: the Québec Family Study.

Shared genetic and familial environmental causes for the associations among resting metabolic rate (RMR), fat-free mass (FFM), and fat mass (FM) were investigated in families participating in phase 2 of the Québec Family Study. A multivariate familial correlation model assessing the pattern of significant cross-trait correlations between family members (e.g., RMR in parents with FFM in offspring) was used to infer the etiology of the associations. For each of FM and FFM with RMR, significant sibling, parent-offspring, and intraindividual cross-trait correlations suggests the associations are familial. Furthermore, the lack of significant spouse cross-trait correlations suggests that the familial aggregation is primarily genetic. Bivariate heritability estimates suggest that as much as 45% to 50% of the shared variance between FFM and RMR may be genetic, and as much as 28% to 34% for FM and RMR. This study supports the notion that the gene(s) affecting each of FFM and FM also influence the RMR. Moreover, the lack of any familial associations between FFM and FM suggests that the effects of each body size component on RMR are independent, i.e., more than one genetic source on the RMR-body size association. The possibility that RMR is an oligogenic trait (i.e., more than one underlying genetic etiology) should be further investigated using more complex multivariate segregation methods until specific genes can be tested.

Adipose Tissue↗
PubMed1996

Familial clustering of abdominal visceral fat and total fat mass: the Québec Family Study.

The evidence for common familial factors underlying total fat mass (estimated from underwater weighing) and abdominal visceral fat (assessed from CT scan) was examined in families participating in phase 2 of the Québec Family Study (QFS) using a bivariate familial correlation model. Previous QFS investigations suggest that both genetic (major and polygenic) and familial environmental factors influence each phenotype, accounting for between 55% to 71% of the phenotypic variance in fat mass, and between 55% to 72% for abdominal visceral fat. The current study suggests that the bivariate familial effect ranges from 29% to 50%. This pattern suggests that there may be common familial determinants for abdominal visceral fat and total fat mass, as well as additional familial factors which are specific to each. The relatively high spouse cross-trait correlations usually suggest that a large percent of the bivariate familial effect may be environmental in origin. However, if mating is not random, then the spouse resemblance may reflect either genetic or environmental causes, depending on the source [i.e., through similar genes or cohabitation (environmental) effects]. Finally, there are significant sex differences in the magnitude of the familial cross-trait correlations involving parents, but not offspring, suggesting complex generation (i.e., age) and sex effects. For example, genes may turn on or off as a function of age and sex, and/or there may be an accumulation over time of effects due to the environment which may vary by sex. Whether the common familial factors are genetic (major and/or polygenic), environmental, or some combination of both, and whether the familial expression depends on sex and/or age warrants further investigation using more complex models.

Abdomen↗
PubMed1996

Familial correlations in the Québec family study: cross-trait familial resemblance for body fat with plasma glucose and insulin.

This study represents one component in our investigation of the familial factors underlying the insulin resistance (or metabolic) syndrome involving obesity, hyperinsulinaemia, glucose intolerance, dyslipidaemia, and hypertension. Here we examine the cross-trait familial resemblance between four measures of body size (two assessing total fat [body mass index and sum of six skinfolds] and two assessing fat patterning [ratio of trunk skinfold sum to extremity skinfold sum, adjusted and unadjusted for total subcutaneous fat]) with fasting plasma levels of glucose, insulin, and the ratio of insulin to glucose (IGR) in non-diabetic families participating in phase 1 of the Québec Family Study. A bivariate familial correlation model assessed both intraindividual (e.g. father's body size with father's insulin) and interindividual (e.g. father's body size with son's insulin) cross-trait associations. Intraindividual correlations suggested a greater degree of cross-trait associations for body fat (rather than fat distribution) measures with insulin and the IGR (rather than with glucose) levels. While the intraindividual correlations were significant for most cross-trait comparisons, only the sum of six skinfolds evidenced any familial association (i.e. interindividual resemblance) with insulin and the IGR. Specifically, cross-trait parent-offspring (but not sibling or spouse) correlations were significant, with a bivariate familiality estimate (i.e. polygenic and/or common familial environment) of about 8%. While the lack of sibling correlations does not suggest a simple familial hypothesis, a more complex genetic effect underlying the common covariation between total body fat with insulin and IGR cannot be ruled out.

Adolescent↗