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C Bouchard

Publications and source records attributed to C Bouchard.

At least 91 records · Page 5Linked to original sources
PubMed2001

Evidence of LPL gene-exercise interaction for body fat and LPL activity: the HERITAGE Family Study.

Evidence of a gene-exercise interaction for traits related to body composition is limited. Here, the association between the lipoprotein lipase (LPL) S447X polymorphism and changes in body mass index, fat mass, percent body fat, abdominal visceral fat measured by computed tomography, and post-heparin plasma LPL activity in response to 20 wk of endurance training was investigated in 741 adult white and black subjects. Changes were compared between carriers and noncarriers of the X447 allele after adjustment for the effects of age and pretraining values. No evidence of association was observed in men. However, white women carrying the X447 allele exhibited greater reductions of body mass index (P = 0.01), fat mass (P = 0.01), and percent body fat (P = 0.03); in black women, the carriers exhibited a greater reduction of abdominal visceral fat (P = 0.05) and a greater increase in post-heparin LPL activity (P = 0.02). These results suggest that the LPL S447X polymorphism influences the training-induced changes in body fat and post-heparin LPL activity in women but not in men.

Adult↗
PubMed2001

TGF-beta(1) gene-race interactions for resting and exercise blood pressure in the HERITAGE Family Study.

We examined the possible association between a transforming growth factor (TGF)-beta(1) gene polymorphism in codon 10 and blood pressure (BP) at rest, in acute response to exercise in the pretrained (sedentary) and trained states, as well as in its training response (Delta) to 20 wk of endurance exercise. Subjects were 257 black and 480 white, healthy sedentary normotensive subjects from the HERITAGE Family Study. The polymorphism was detected by polymerase chain reaction and digestion with the Msp A1 I endonuclease yielding a wild (leucine-10) and a mutant (proline-10) allele. Resting and exercise [50 W plus 60, 80, and 100% maximal oxygen consumption (VO(2)(max))] BP were determined before and after training. Significant (P < 0.05) race-genotype interactions were found for systolic (S) BP in both the sedentary and trained states. Among whites but not in blacks, the TGF-beta(1) genotypes were significantly (P < 0.05) associated with sedentary-state SBP at rest, at 50 W, and at 60 and 100% VO(2)(max)as well as with trained-state SBP at rest and at 80 and 100% VO(2)(max). The leucine-10 homozygotes had significantly (P < 0.05) lower SBP than proline-10 homozygotes. DeltaBP was not significantly associated with genotype. These results support the hypothesis of an association between the TGF-beta(1) marker in codon 10 and SBP at rest and in response to acute exercise in whites but not in blacks.

Adult↗
PubMed2001

Genomic scan for exercise blood pressure in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study.

Agenome-wide linkage scan was performed for genes affecting submaximal exercise systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the sedentary state and their responses to a standardized endurance training program. A total of 344 polymorphic markers were used, and 344 pairs of siblings from 99 white nuclear families and 102 sibling pairs from 105 black family units were available for the study. All subjects were healthy but sedentary at baseline. SBP and DBP were measured during exercise tests at 2 different intensities: 50 W (SBP50 and DBP50) and 80% of maximal oxygen consumption (SBP80 and DBP80). Baseline blood pressure phenotypes were adjusted for age, gender, and body mass index, and the training responses (after training minus baseline [Delta]) were adjusted for age, gender, baseline body mass index, and baseline blood pressure. Two analytical strategies were used: a multipoint variance-components linkage analysis using all the family data and a single-point linkage analysis using pairs of siblings. In whites, promising linkages (lod score >1.75) were detected for baseline SBP80 on 10q23-q24 and for DeltaSBP50 on 8q21. In addition, several chromosomal regions with suggestive evidence of linkage (lod score 1.0 to 1.75) were observed for SBP50 (22q11.2-q13), DBP50 (6q23-q27), SBP80 (2p24, 2q21, 14q11.1-q12, and 16q21), DBP80 (6q13-q21), DeltaSBP50 (7p12-p13), and DeltaDBP50 (5q31-q32). In blacks, DBP50, DBP80, and DeltaDBP80 showed promising quantitative trait loci on 18p11.2, 11q13-q21, and 10q21-q23, respectively. Suggestive linkages were evident for DBP50 on 2p22-p25, 11p15.5, and 18q21.1; for SBP80 on 6q21-q21, 6q31-q36, 12q12-q13, 15q12-q13, and 17q11-q12; and for DBP80 on 8q24, 10q21-q24, and 12p13. All the detected chromosomal regions include several potential candidate genes and therefore warrant further studies in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) cohort and other studies.

Blood Pressure↗
PubMed2001

Effects of endurance exercise training on plasma HDL cholesterol levels depend on levels of triglycerides: evidence from men of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study.

High density lipoprotein (HDL) cholesterol concentrations have been shown to increase with regular endurance exercise and, therefore, can contribute to a lower risk of coronary heart disease in physically active individuals compared with sedentary subjects. Although low HDL cholesterol levels are frequently observed in combination with hypertriglyceridemia, some individuals may be characterized by isolated hypoalphalipoproteinemia, ie, low HDL cholesterol levels in the absence of elevated triglyceride (TG) concentrations. The present study compared the responses of numerous lipoprotein-lipid variables to a 20-week endurance exercise training program in men categorized on the basis of baseline TG and HDL cholesterol concentrations: (1) low TG and high HDL cholesterol (normolipidemia), (2) low TG and low HDL cholesterol (isolated low HDL cholesterol), (3) high TG and high HDL cholesterol (isolated high TGs), and (4) high TGs and low HDL cholesterol (high TG/low HDL cholesterol). A series of physical and metabolic variables was measured before and after the training program in a sample of 200 men enrolled in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. At baseline, men with high TG/low HDL cholesterol had more visceral adipose tissue than did men with isolated low HDL cholesterol and men with normolipidemia. The 0.4% (not significant) exercise-induced increase in HDL cholesterol levels in men with isolated low HDL cholesterol suggests that they did not benefit from the "HDL-raising" effect of exercise. In contrast, men with high TG/low HDL cholesterol showed a significant increase in HDL cholesterol levels (4.9%, P<0.005). Whereas both subgroups of men with elevated TG levels showed reductions in plasma TGs ( approximately -15.0%, P<0.005), only those with high TG/low HDL cholesterol showed significantly reduced apolipoprotein B levels at the end of the study (-6.0%, P<0.005). Multiple regression analyses revealed that the exercise-induced change in abdominal subcutaneous adipose tissue (10.6%, P<0.01) was the only significant correlate of the increase in plasma HDL cholesterol with training in men with high TG/low HDL cholesterol. Results of the present study suggest that regular endurance exercise training may be particularly helpful in men with low HDL cholesterol, elevated TGs, and abdominal obesity.

Adult↗
PubMed2001

G-308A polymorphism of the tumor necrosis factor alpha gene promoter and salivary cortisol secretion.

The objective of the current study was to examine the potential impact of the G-->A substitution at position -308 of the tumor necrosis factor alpha (TNF-alpha) gene promoter on 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 the 5' untranslated region of the TNF-alpha gene followed by digestion with the restriction enzyme NcoI. The frequencies were 0.77 for allele G and 0.23 for allele A. Tests for differences in salivary cortisol levels between the TNF-alpha genotypes revealed that there were significantly higher cortisol levels in the morning, before as well as 30 and 60 min after stimulation by a standardized lunch in homozygotes for the rare allele in comparison with the other genotypes. In addition, homozygotes for the rare allele had a tendency toward higher mean values of body mass index, waist to hip ratio, and abdominal sagittal diameter compared with the other genotype groups. The results also indicated a weak trend toward elevated insulin and glucose levels among men with the A/A genotype. In conclusion, a G-->A polymorphism in the 5' untranslated region of the TNF-alpha gene is associated with elevated morning cortisol levels as well as elevated postprandial cortisol secretion. This increase in cortisol secretion might be the endocrine mechanism underlying the previously observed associations between the NcoI TNF-alpha polymorphism and obesity as well as insulin resistance. However, to what extent this polymorphism is associated with these conditions is uncertain from the present data.

Alleles↗
PubMed2001

Leptin receptor gene polymorphisms are associated with insulin in obese women with impaired glucose tolerance.

Leptin receptors are present on beta-cells as well as on muscle and fat cells, thus enabling leptin to modulate both insulin secretion and insulin action. Leptin inhibits especially the glucose-stimulated insulin secretion from pancreatic cells. The leptin receptor (LEPR) gene could thus play a role in the regulation of glucose and insulin after an oral glucose load. Therefore, the relationship between LEPR polymorphisms and glucose and insulin response to an oral glucose tolerance test (OGTT) was investigated. Three LEPR polymorphisms (Lys(109)Arg, Gln(223)Arg, and Lys(656)Asn) were typed on genomic DNA of 358 overweight and obese women, aged 18-60 yr. Based on an OGTT, 269 subjects were defined with normal glucose tolerance, and 89 with impaired glucose tolerance (IGT). Associations between genotypes and glucose metabolism were analyzed with a general linear models procedure in pre- and postmenopausal women separately, after adjusting the data for age and fat mass. In postmenopausal women with IGT (n = 24), associations were found with Lys(109)Arg and Lys(656)Asn for fasting insulin (P = 0.05) and with Lys(109)Arg and Gln(223)Arg for the insulin response to an OGTT (P < 0.02). In the same group, trends were found with Lys(656)Asn for fasting glucose as well as in response to the OGTT. In premenopausal women with IGT (n = 65), associations were found with Lys(109)Arg and Lys(656)Asn for overall glucose response to the glucose load. In contrast, no associations with insulin or glucose were found in women with normal glucose tolerance. In conclusion, these data indicate that LEPR polymorphisms are associated with insulin and glucose metabolism in women with impaired glucose homeostasis.

Adolescent↗
PubMed2001

Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors.

Numerous physiological factors modulate GH secretion, but these variables are not independent of one another. We studied 40 younger (20-29 yr.; 21 men and 19 women) and 62 older (57-80 yr.; 35 men and 27 women) adults to determine the contributions of several demographic and physiological factors to the variability in integrated 24-h GH concentrations. Serum GH was measured every 10 min for 24 h in an enhanced sensitivity chemiluminescence assay. The predictor variables included: age group (young or old), gender, abdominal visceral fat (by computed tomography), total body fat mass and percentage body fat by dual-energy x-ray absorptiometry, serum IGF-I, fasting serum insulin, 24-h mean estradiol and testosterone, and peak oxygen uptake by graded exercise (treadmill) testing. Multiple ordinary least squares regression analysis was used to quantitatively assess the individual contribution that each predictive measure made to explain the variability among values of integrated 24-h GH concentrations while in the presence of the remaining predictors. The model explained 65% of the variance in integrated 24-h GH concentrations. Abdominal visceral fat (P < 0.002) and fasting insulin (P < 0.008) were consistently important predictors of integrated 24-h GH concentrations independent of age group, gender, and all other predictor variables. Although serum IGF-I was an important overall predictor of integrated 24-h GH concentrations (P = 0.002), this relationship was present only in the young subjects and was modulated by gender. The remaining variables failed to contribute significantly to the model. We conclude that abdominal visceral fat and fasting insulin are important predictors of integrated 24-h GH concentrations in healthy adults, independent of age and gender. Serum IGF-I is an important predictor of integrated 24-h GH concentrations in young but not older subjects. Bidirectional feedback between each of these three factors and GH secretion may account for the strong relationships observed.

Abdomen↗
PubMed2001

Mutations in the preproghrelin/ghrelin gene associated with obesity in humans.

Ghrelin and preproghrelin sequences were determined in 96 unrelated female subjects with severe obesity (mean body mass index (BMI) 42.3 +/- 3.4 kg/m(2)) and in 96 non-obese female controls (mean BMI 23.0 +/- 1.4 (kg/m2) of the Swedish Obese Subjects cohort. A mutation at amino acid position 51 (Arg51Gln) of the preproghrelin sequence that corresponds to the last amino acid in mature ghrelin product was identified in six (all heterozygotes) obese subjects (6.3%) but not among controls (p < 0.05). The self-reported weight at 20, 30, and 40 years of age tended to be 7.5, 4.7 and 6.4 kg lower, respectively, among obese Gln allele carriers versus obese non-carriers. In addition, a mutation at codon 72 of the preproghrelin gene (Leu72Met) was detected in 15 obese (12 hetero- and 3 homozygotes) and 12 control (all heterozygotes) subjects. This mutation outside the coding region of the mature ghrelin product tended to be associated with lower age of self-reported onset of obesity (15.6 +/- 7.9 vs. 20.5 +/- 10.5 years; p = 0.09). In addition to these two mutations in coding regions, a G274A base change in a non-coding region between exons one and two was found only in two obese individuals. The Arg51Gln amino acid substitution may alter the cleavage site of endoproteases and the length of the mature ghrelin product. The functional significance of the Leu72Met mutation and a G274A base change remains to be determined. In conclusion, the data provide evidence that a low frequency sequence variation in the ghrelin gene could play a role in the etiology of obesity.

Adult↗
PubMed2001

Plasma ghrelin concentration and energy balance: overfeeding and negative energy balance studies in twins.

Central (intracerebral ventral) and peripheral (subcutaneous and intraperitoneal) administration of ghrelin causes obesity in rodents by increasing food intake and decreasing fat oxidation. Recent studies in humans have shown that plasma ghrelin concentration was inversely related to body fat and was lower in Pima Indians, a population susceptible to obesity. Whether ghrelin plays a role in the etiology of obesity in humans is unknown. We, therefore, measured plasma ghrelin concentration before and after two interventions in monozygotic twins previously studied at Laval University, Quebec City. Twelve pairs of monozygotic twins were overfed by 84,000 kcal over a 100-day period, whereas another seven pairs of monozygotic twins were submitted to a 53,000 kcal negative energy balance induced by exercise over a 93-day period. At baseline, for all the subjects, plasma ghrelin concentration was negatively correlated with body mass and body fatness (r varying from 0.36 to 0.45). The intraclass coefficient for the twin resemblance (r(I) = 0.75; p = 0.006) indicated that plasma ghrelin concentration is a familial trait. In response to the 100-day intervention, plasma ghrelin exhibited a non-significant decrease of 61 +/- 30 fmol/l (p = 0.18) with overfeeding and a non-significant increase of 58 +/- 34 fmol/l (p = 0.17) with negative energy balance. However, there was no relationship between baseline plasma ghrelin concentration and the magnitude of body weight change in both interventions. These first experimental data under "clamped energy balance conditions" do not provide evidence that plasma ghrelin is involved in the etiology of human obesity. However, studies in free-living individuals are needed to clarify this question.

Adipocytes↗
PubMed2001

Age, body mass index, race and other determinants of steroid hormone variability: the HERITAGE Family Study.

OBJECTIVE AND METHODS: To investigate from the HERITAGE Family Study database, 13 steroid hormones (androstane-3alpha, 17beta-diol glucuronide, androsterone glucuronide, cortisol, dehydroepiandrosterone (DHEA), DHEA ester (DHEAE), DHEA sulfate (DHEAS), dihydrotestosterone (DHT), estradiol, 17-hydroxyprogesterone, progesterone, pregnenolone ester, sex hormone binding globulin (SHBG) and testosterone in each sex for their relationships with age, body mass index (BMI), race and key lifestyle variables. Sample sizes varied from 676 to 750 per hormone. Incremental regression methods were used to examine the contributions of the variables to steroid hormone variability. RESULTS: Age was a major predictor for most steroid hormones. The greatest contribution of age was a negative relationship with DHEAS (R(2)=0.39). BMI was also associated with the variability of several steroid hormones, being the most important predictor of SHBG (R(2)=0.20) and of testosterone (R(2)=0.12) concentrations. When age and BMI were included, race still contributed significantly to the variations in cortisol (R(2)=0.02 for men and 0.04 for women), DHT (R(2)=0.02 for men and 0.03 for women), and progesterone (R(2)=0.03 for women). Nevertheless, race appeared to be less important than age and BMI. In addition, lifestyle indicators (food and nutrient intakes, smoking and physical activity) influenced steroid hormone variability. Their contributions, however, were minor in most cases once age, BMI and race had been taken into account. CONCLUSIONS: We conclude that age was the most important factor, followed by BMI, race and lifestyle factors in explaining steroid hormone variability.

Adolescent↗
PubMed2001

Familial resemblance for free androgens and androgen glucuronides in sedentary black and white individuals: the HERITAGE Family Study. Health, Risk Factors, Exercise Training and Genetics.

Familial correlation analyses were used to evaluate the familial aggregation of plasma androgens and androgen glucuronides (testosterone (TESTO), dihydrotestosterone (DHT), androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G), and androsterone glucuronide (ADT-G)) in 505 members of 99 white families and 296 members of 111 black families participating in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. Each of these four measures was determined by RIA after separation of conjugated and unconjugated steroid using C18 column chromatography. All participants were sedentary prior to being including in this study. Significant spouse correlations, as well as parent-offspring and sibling correlations, were found for TESTO, DHT, 3 alpha-DIOL-G, and ADT-G in the white sample, suggesting that common familial environments and genes contribute to the familial resemblance. In the black sample, significant sibling and parent-offspring correlations were found for all four phenotypes, while the spouse correlation was marginally significant for 3 alpha-DIOL-G and not significant for TESTO, DHT, and ADT-G. The non-significance of spouse correlations in the black individuals may be due to the small number of spouse pairs. The maximal heritability estimates of TESTO, DHT, 3 alpha-DIOL-G, and ADT-G were 69%, 87%, 74%, and 56% for white individuals and 70%, 73%, 62%, and 48% for black individuals respectively. Sex differences in heritability estimates were found in the white individuals, but they were less dramatic in the black individuals. In conclusion, plasma levels of androgens and androgen glucuronides are highly heritable in both white individuals and black individuals. There are notable sex differences in the white individuals.

Adolescent↗
PubMed2001

A genome-wide scan for abdominal fat assessed by computed tomography in the Québec Family Study.

To identify chromosomal regions harboring genes influencing the propensity to store fat in the abdominal area, a genome-wide scan for abdominal fat was performed in the Quebec Family Study. Cross-sectional areas of the amount of abdominal total fat (ATF) and abdominal visceral fat (AVF) were assessed from a computed tomography scan taken at L4-L5 in 521 adult subjects. Abdominal subcutaneous fat (ASF) was obtained by computing the difference between ATF and AVF. The abdominal fat phenotypes were adjusted for age and sex effects as well as for total amount of body fat (kilogram of fat mass) measured by underwater weighing, and the adjusted phenotypes were used in linkage analyses. A total of 293 microsatellite markers spanning the 22 autosomal chromosomes were typed. The average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were available for single-point (SIBPAL) and 156 families for multipoint variance components (SEGPATH) linkage analyses. The strongest evidence of linkage was found on chromosome 12q24.3 between marker D12S2078 and ASF (logarithm of odds [LOD] = 2.88). Another marker (D12S1045) located within 2 cM of D12S2078 also provided evidence of sib-pair linkage with ASF (P = 0.019), ATF (P = 0.015), and AVF (P = 0.0007). Other regions with highly suggestive evidence (P < 0.0023 or LOD > or =1.75) of multipoint linkage and evidence (P < 0.05) of single-point linkage, all for ASF, included chromosomes 1p11.2, 4q32.1, 9q22.1, 12q22-q23, and 17q21.1. Three of these loci (1p11.2, 9q22.1, and 17q21.1) are close to genes involved in the regulation of sex steroid levels, whereas two others (4q32.1 and 17q21.1) are in the proximity of genes involved in the regulation of food intake. This first genome-wide scan for abdominal fat assessed by computed tomography indicates that there may be several loci determining the propensity to store fat in the abdominal depot and that some of these loci may influence the development of diabetes in obese subjects.

Adipose Tissue↗
PubMed2001

Decreased fasting and oral glucose stimulated C-peptide in nondiabetic subjects with sequence variants in the sulfonylurea receptor 1 gene.

The high-affinity sulfonylurea receptor 1 (SUR1) plays an important role in regulating insulin secretion. In the Québec Family Study, we genotyped 731 individuals (685 nondiabetic [ND] subjects) for the SUR1 gene IVS15-3c-->t and exon 18 Thr759(ACC-->ACT) polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism analysis. Phenotypes measured were fasting plasma glucose (GLU), fasting plasma insulin (INS), and fasting C-peptide (CPEP), as well as oral glucose tolerance test (OGTT) responses; they were adjusted for age, sex, waist circumference, and the sum of six skinfold thicknesses. In ND subjects, exon 18 Thr759(ACC-->ACT) T allele carriers (T+) had lower CPEP (P = 0.022, -12.8%) and acute C-peptide responses (area above basal in first 30 min [CP30]) (P = 0.051, -12.4%) than noncarriers (T-). Also, in those with the cT/tC haplotype (from both IVS15-3c-->t and exon 18 Thr759[ACC-->ACT] polymorphisms), CPEP (P = 0.005, -21.2%), CP30 (P = 0.034, -19.2%), and total C-peptide responses (P = 0.016, -20.2%) were lower than that in cT- subjects. In overweight individuals (BMI >25 kg/m2), differences between carriers and noncarriers of the T or cT alleles were greater for GLU (P = 0.023-0.034), CPEP (P = 0.021-0.015), acute OGTT insulin response (P = 0.014-0.019), and CP30 (P = 0.034-0.019). These results suggest that the T and cT allele variants are associated with lower insulin secretion parameters, particularly in female and overweight subjects, adding evidence to the role of SUR1 sequence variants in decreased insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed2001

Clustering of metabolic abnormalities in obese individuals: the role of genetic factors.

The objective of this paper is to review the current evidence in support of genetic factors underlying the clustering of components of the metabolic syndrome in obese individuals. It has become clear that individual features of the metabolic syndrome are partially determined by familial factors some of which are unique to a given component and others that are shared among several features. A few candidate genes, encoding proteins of glucose, insulin and lipid metabolism, lipolytic cascade, fatty acid intestinal absorption, glucocorticoid metabolism, haemostasis and blood pressure, have been associated with a clustering of metabolic abnormalities, although the functional significance of these associations remains to be established. Furthermore, genetic polymorphisms, such as those detected at several lipoprotein metabolism loci, can modulate the relationships between different components of the metabolic syndrome. An overfeeding study conducted on identical twins has demonstrated that genetic factors play an important role in the responsiveness to changing energy balance conditions. Leptin receptor, beta2 adrenergic receptor and glucocorticoid receptor gene polymorphisms have been associated with an augmented clustering of metabolic abnormalities in response to overfeeding. Gene-gene interaction effects between markers of the alpha2A, beta2 and beta3 adrenergic receptor genes on components of the metabolic syndrome have been described. Genetic factors also seem to modify the responsiveness of metabolic syndrome features to endurance training. A growing understanding of the genetic architecture of the metabolic syndrome may help in the prevention of this condition. The reduction of excess body fat, the most common clinical feature among the cluster of metabolic abnormalities, should be the focus of the prevention and treatment of the metabolic syndrome.

Adipose Tissue↗
PubMed2001

Managing atypical squamous cells of undetermined significance in Papanicolaou smears.

OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.

Adolescent↗
PubMed2001

Association between uncoupling protein 3 gene and obesity-related phenotypes in the Québec Family Study.

BACKGROUND: UCP3 is a mitochondrial membrane transporter that is postulated to uncouple oxidative phosphorylation from ATP synthesis producing heat instead of ATP. Human UCP3 is mainly expressed in skeletal muscle, which plays an important role in energy homeostasis and substrate oxidation. Therefore, UCP3 is a good candidate gene for obesity. MATERIALS AND METHODS: We analyzed, among 734 subjects from the Québec Family Study, a new GA repeat microsatellite located in intervening sequence (IVS) 6 (GAIVS6) in UCP3 gene, and two already described restriction fragment length polymorphisms (RFLP) Y210Y(C-->T) and V102I(G-->A). Covariance analysis across genotypes for different adiposity, resting energy expenditure, and glucose metabolism variables was undertaken with age and sex, plus body fat and body mass for nonadiposity phenotypes, as covariates. RESULTS: We found strong associations between GAIVS6 and body mass index (p = 0.0001), fat mass (p = 0.0005), percentage body fat (p = 0.0004), the sum of six skinfold thickness (p = 0.0001), and leptin level (p = 0.0001). Homozygote for the GAIVS6 240 bp alleles (15% frequency in QFS) showed higher adiposity than subjects with the GAIVS6 238 bp allele (70% in QFS). The exons, the 5' untranslated region (UTR), and the exon-intron junctions of UCP3 gene from subjects homozygote for either GAIVS6 238 bp or 240 bp alleles were sequenced in search for mutations. Variants 5'UTR-55C-->T and Y210Y(C-->T) were detected, whereas IVS4-36C-->T was uncovered, but no new exonic or splice junction mutation was observed. RFLP Y210Y(C-->T) was not associated to adiposity in QFS; V1021(G-->A) showed no variation. CONCLUSION: Our results suggest that some alleles of UCP3 are involved in the etiology of human obesity.

5' Untranslated Regions↗
PubMed2001

Familial aggregation of seven-year changes in blood pressure in Canada.

OBJECTIVE: To determine the familial resemblance for baseline and seven-year changes in blood pressure in the Canadian population. METHODS: The study participants were 857 people from 348 families in the 1988 Campbell's Survey, which was a seven-year follow-up of the Canada Fitness Survey. Systolic and diastolic blood pressures were measured at baseline and at follow-up, and were adjusted for age and body mass index by using regression analysis. Familial correlation models were fit to the data by using path analysis, and maximal heritabilities were calculated from the most parsimonious models. RESULTS: There was significant familial resemblance for baseline blood pressure and changes in blood pressure. In general, all classes of familial correlations (spousal, parent-offspring and sibling) were significant and were of comparable magnitude. The maximal heritabilities, which are influenced to an unknown degree by genes and shared environmental factors, were 50% and 70% for diastolic and systolic blood pressures, respectively, and 66% and 41% for seven-year changes in diastolic and systolic blood pressures, respectively. CONCLUSIONS: There is significant familial aggregation for blood pressure and for natural changes in blood pressure in the Canadian population. Genes may be important in explaining the familial resemblance for blood pressure; however, the presence of significant spousal correlations suggests that shared lifestyle and family environments are also important factors in the familial aggregation.

Adolescent↗