Biomedical subjects

L Pérusse

Publications and source records attributed to L Pérusse.

At least 19 recordsLinked to original sources

PubMed2006

Features of the metabolic syndrome are modulated by an interaction between the peroxisome proliferator-activated receptor-delta -87T>C polymorphism and dietary fat in French-Canadians.

OBJECTIVE: We verified whether genetic variants in this gene are associated with the MS and whether dietary fatty acids interact with the -87T>C polymorphism. METHODS: By direct sequencing, we identified 15 variants in the PPAR-delta gene and analyses were pursued with the -87T>C polymorphism for 340 subjects. RESULTS: Metabolic variables were comparable among each genotype group. The -87T>C polymorphism, fat intake and the interaction accounted, respectively for 2.2, 1.9 and 1.5% of the variance in high-density lipoprotein cholesterol (HDL-C) levels (P<0.05) (age, sex and energy intake were included into the model). The total cholesterol/HDL-C ratio was also modulated by a gene-diet interaction and by the -87T>C polymorphism (P<0.05). No gene-diet interaction effects were observed for other features of the MS. The age- and sex-adjusted odds ratio (OR) of exhibiting three or more features of the MS when carrying the -87C allele was 0.62 (P=0.04) compared to -87T/T. However, in subjects consuming less than 34.4% of energy from fat (median of fat consumption), the OR in carriers of the -87C allele was of 0.42 (P=0.008). CONCLUSION: These data suggest that the PPAR-delta -87T>C polymorphism may be associated with a lower risk to exhibit the MS and this association is influenced by dietary fat intake. The metabolic syndrome (MS) is influenced by genetic and environmental factors. Peroxisome proliferator-activated receptor delta (PPAR-delta), a transcription factor involved in lipid metabolism, is a candidate gene for the MS.

Adult↗

PubMed2006

Muscle adiposity and body fat distribution in type 1 and type 2 diabetes: varying relationships according to diabetes type.

OBJECTIVE: To compare the relationships between markers of total and regional adiposity with muscle fat infiltration in type 1 diabetic and type 2 diabetic subjects and their respective nondiabetic controls, and to document these relationships in type 1 diabetic subjects. DESIGN: Cross-sectional study. SUBJECTS: In total, 86 healthy, with type 1 diabetes, type 2 diabetes or control subjects. Each diabetic group was matched for age, sex and body mass index with its respective nondiabetic control group. MEASUREMENTS: Measures of body composition (hydrodensitometry), fat distribution (waist circumference, abdominal and mid-thigh computed tomography scans) and blood lipid profiles were assessed. RESULTS: Low attenuation mid-thigh muscle surface correlated similarly with markers of adiposity and body composition in all groups, regardless of diabetes status, except for visceral adipose tissue and waist circumference. Indeed, relationships between visceral adiposity and muscle adiposity were significantly stronger in type 2 vs type 1 diabetic subjects (P<0.05 for comparison of slopes). In addition, in well-controlled type 1 diabetic subjects (mean HbA(1c) of 6.8%), daily insulin requirements tended to correlate with low attenuation mid-thigh muscle surface, a specific component of fat-rich muscle (r=0.36, P=0.08), but not with glycemic control (HbA(1c)). CONCLUSION: This study suggests that the relationship of central adiposity and muscle adiposity is modulated by diabetes status and is stronger in the insulin resistant diabetes type (type 2 diabetes). In well-controlled nonobese type 1 diabetic subjects, the relationship between muscle fat accumulation and insulin sensitivity was also maintained.

Adiposity↗

PubMed2006

Polymorphisms in the leptin and leptin receptor genes in relation to resting metabolic rate and respiratory quotient in the Québec Family Study.

BACKGROUND: Leptin (LEP) is an endocrine hormone that participates in many metabolic pathways, including those associated with the central regulation of energy homeostasis. OBJECTIVE: We examined the associations between polymorphisms in the LEP and leptin receptor (LEPR) genes and resting metabolic rate (RMR) and respiratory quotient (RQ) in the Quebec Family Study. METHODS AND SUBJECTS: Three polymorphisms in LEPR (K109R, Q223R and K656N) and one in LEP (19A > G) were genotyped in 678 subjects. RMR, RQ at rest and RQ while sitting, standing and walking at 4.5 km/h (RQ45) were adjusted for age, sex, fat mass and fat-free mass. RESULTS: RQ45 was associated with the LEPR-K109R (P = 0.004) and Q223R (P = 0.03) polymorphisms, and RMR showed association with the LEPR-K656N polymorphism (P = 0.006). For the LEP-19A > G polymorphism, no significant associations were observed. However, LEP-A19A homozygotes who were carriers of the LEPR N656 allele had a significantly lower RQ45 compared to other genotype combinations (P for interaction=0.003). CONCLUSION: These findings suggest that DNA sequence variation in the LEPR gene contributes to human variation in RMR and in the relative rates of substrate oxidation during low-intensity exercise in steady state but not in a resting state.

Adult↗

PubMed2006

An overview of obesity-specific quality of life questionnaires.

The measurement of quality of life in patients with obesity is useful to evaluate the effects of treatment (including bariatric surgery) and may influence the development of clinical pathways, service provision, healthcare expenditures and public health policy. Consequently, clinicians, researchers and policy makers must rely on valid measurement instruments. We reviewed 11 obesity-specific quality of life questionnaires and classified them according to their domain of interest and described their measurement properties (specifications, validity, reliability, responsiveness and interpretability). We found that (i) nine questionnaires were developed specifically to be used as evaluative instruments in clinical trials; (ii) only three targeted populations with morbid obesity (body mass index > 40 kg m(-2)); (iii) construct validity was properly studied in three questionnaires; (iv) demonstration of responsiveness from independent randomized controlled trials was available for two of the 11 questionnaires; (v) keys to interpretation of scores were provided for three questionnaires. Future research should include further validation and a better definition of the interpretability of existing instruments.

Health Status↗

PubMed2005

High normal 2-hour plasma glucose is associated with insulin sensitivity and secretion that may predispose to type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to evaluate differences in insulin sensitivity, insulin secretion and risk factors for cardiovascular disease between subjects with a 2-h plasma glucose (2hPG) level within the normal range (NPG) and subjects with IGT, following a 75-g OGTT. We also aimed to determine the respective contributions made by 2hPG and fasting plasma glucose to the metabolic risk profile. METHODS: We compared cardiovascular risk factors and insulin sensitivity and insulin secretion by using several indices calculated using measurements obtained during an OGTT. Subjects (n=643, age 18-71 years) were participants in the Quebec Family Study and were categorised according to 2hPG as having low NPG (2hPG <5.6 mmol/l, the group median for normal values), high NPG (2hPG 5.6-7.7 mmol/l) or IGT (2hPG 7.8-11.0 mmol/l). Subjects with type 2 diabetes were excluded from all analyses. RESULTS: Beta cell function and insulin sensitivity progressively decreased with increasing 2hPG. Compared with subjects with low NPG, subjects with high NPG were more insulin-resistant (p<0.05) and had reduced insulin secretion (adjusted for insulin resistance) (p<0.001). They also had higher plasma triglyceride concentrations (p<0.01) and cholesterol:HDL cholesterol ratios (p<0.05). These differences remained even after adjustment for age, sex, BMI and waist circumference. Multivariate analyses showed that 2hPG was closely associated with risk factors for diabetes and with cardiovascular variables, including triglycerides (p<0.0001) and apolipoprotein B (p<0.01). CONCLUSIONS/INTERPRETATION: These results show that deteriorations in glucose-insulin metabolism, which may predispose individuals to type 2 diabetes and cardiovascular disease, are already present in subjects with 2hPG concentrations within the high normal range. Independently of obesity, 2hPG was found to explain, in part, the variance observed in cardiovascular and diabetes risk factors. In addition, elevated 2hPG was associated with metabolic alterations that appear to be the most detrimental to metabolic health. Thus, 2hPG values within the high normal range may be an important marker for the identification of people at risk of complications related to type 2 diabetes.

Adolescent↗

PubMed2005

Melanocortin-4 receptor gene and physical activity in the Québec Family Study.

UNLABELLED: Physical inactivity is a risk factor for numerous chronic diseases. Low compliance with interventions to increase activity suggests involvement of biological systems. OBJECTIVE: To examine whether sequence variants in genes encoding neuropeptides and receptors in the arcuate and paraventricular nucleus of the hypothalamus contribute to variations in physical activity level in the Québec Family Study. METHODS: We genotyped polymorphisms in the melanocortin-4 receptor (MC4R), melanocortin-3 receptor (MC3R), neuropeptide-Y (NPY), neuropeptide-Y Y1 receptor (NPY Y1R), cocaine- and amphetamine-regulated transcript (CART), agouti-related protein (AGRP), and pro-opiomelanocortin (POMC) genes in 669 subjects (age (X+/-s.d.): parents: 52+/-3.4 y; offspring: 28+/-8.7 y). Total physical activity, moderate-to-strenuous activity, and inactivity phenotypes were estimated from a three-day record. The past year's physical activity level was assessed from a questionnaire. Associations between the physical activity phenotypes and the polymorphisms were analyzed using the MIXED model (SAS). RESULTS: The MC4R-C-2745T variant showed significant associations with physical activity phenotypes. The lowest moderate-to-strenuous activity scores (P = 0.005) and the highest inactivity scores (P = 0.01) emerged in the T/T genotype. Exclusion of obese subjects increased the association. For inactivity, the association of the MC4R-C-2745T variant was strongest in the offspring (P = 0.002). The T/T offspring had both the highest inactivity score and the lowest body mass index. The CART-A1475G variant modified the associations with MC4R-C-2745T; T/T homozygotes had the lowest activity scores when they also had the A/A CART-A1475G genotype. No significant associations were observed with polymorphisms in the other neuropeptides. CONCLUSION: These findings suggest that DNA sequence variation at the MC4R gene locus may contribute to the propensity to be sedentary.

Chi-Square Distribution↗

PubMed2005

Haplotypes in the phospholipid transfer protein gene are associated with obesity-related phenotypes: the Québec Family Study.

BACKGROUND: The phospholipid transfer protein (PLTP) may play a role in body fat regulation. OBJECTIVE: To investigate the association between PLTP genetic variants and obesity-related phenotypes. METHODS: Two intronic variants, one in intron 1 (c.-87G>A) and the other in intron 12 (c.1175+68T>G), were genotyped in 811 participants of the Québec Family Study. Nine obesity-related phenotypes were investigated, including body mass index (BMI), obesity (BMI> or =30 kg/m(2)), and waist circumference, percentage of fat, fat mass and fat-free mass measured by hydrostatic weighing as well as total, visceral and subcutaneous abdominal adipose tissue areas assessed by computed tomography. Single markers and haplotypes were tested for associations in family-based designs using the FBAT program. RESULTS: The SNP located in intron 1 showed significant associations with obesity, BMI, waist circumference and fat-free mass (P<0.05). The low-frequency allele (A allele) was associated with higher trait values, suggesting that the transmission of this allele is associated with an increased risk of being obese. Significant associations were observed between haplotypes and obesity, waist circumference, percentage of fat and fat-free mass (P<0.05). The transmission of the AT haplotype (frequency=0.180) was positively associated with obesity-related phenotypes. After sequencing the promoter and the coding regions of the PLTP gene, we were unable to identify a mutation that could replicate these results. CONCLUSION: Intronic variants of the PLTP gene are significantly associated with obesity-related phenotypes. Considering the number and the relevance of candidate genes surrounding the PLTP locus and the absence of missense polymorphisms in the coding region, the associations could be mediated by a second gene allele in linkage disequilibrium with the marker locus.

Adult↗

PubMed2004

Human resistin gene polymorphism is associated with visceral obesity and fasting and oral glucose stimulated C-peptide in the Québec Family Study.

Obesity and insulin resistance are common features of Type 2 Diabetes. A new protein called resistin has been shown to be secreted by adipocytes in mice and to influence insulin sensitivity. The goal of the present study was to investigate the associations between one polymorphism (g-420C>G) of the human resistin gene and phenotypes related to adiposity and glucose metabolism. We genotyped 725 (including 42 diabetics) adult subjects participating in the Quebec Family Study (QFS) by a minisequencing method. Forty-two were diabetic subjects. Phenotypes measured were: body mass index (BMI) and waist circumference (WC), % body fat (PFAT) and fat mass (FM) assessed by under water weighing, abdominal total, subcutaneous and visceral fat assessed by computed tomography and fasting plasma glucose, insulin and C-peptide and their responses to an oral glucose tolerance test (OGTT). Comparisons between genotypes were performed in non-diabetic men (no.=280) and women (no.=403) separately by analyses of covariance (ANCOVA). Among men, g-420 G homozygotes had less visceral fat (p < 0.05), lower levels of acute insulin responses to an OGTT and lower levels of C-peptide in a fasting state and in responses to an OGTT than carriers of the C allele (p < 0.01). These associations were independent of age and adiposity but were not observed in women. These results suggest that in men, the human resistin gene is associated with reduced amount of visceral obesity and lower insulin secretory responses to a glucose load.

Abdomen↗

PubMed2004

Plasma concentrations of apolipoprotein B are modulated by a gene--diet interaction effect between the LFABP T94A polymorphism and dietary fat intake in French-Canadian men.

Hyperapobetalipoproteinemia is a common feature of the metabolic syndrome and could result from the interaction between genetic and dietary factors. The objective of this study was to verify whether dietary fat intake interacts with the T94A polymorphism of the liver fatty acid-binding protein (LFABP) gene to modulate plasma apolipoprotein (apo) B levels. Dietary fat and saturated fat intakes were obtained by a dietitian-administered food frequency questionnaire and the LFABP T94A genotype was determined by a PCR-RFLP based method in 623 French-Canadian men recruited through the Chicoutimi Lipid Clinic (279 T94/T94, 285 T94/A94, and 59 A94/A94). The LFABP T94A polymorphism was not associated with plasma apo B levels when fat intake was not taken into consideration. However, in a model including the polymorphism, fat intake expressed as a percentage of total energy intake, the interaction term and covariates, the variance in apo B concentrations was partly explained by the LFABP T94A polymorphism (5.24%, p = 0.01) and by the LFABP T94A*fat interaction (6.25%, p = 0.005). Results were similar when saturated fat replaced fat intake in the model (4.49%, p = 0.02 for LFABP T94A and 6.43%, p = 0.004 for the interaction). Moreover, in men consuming more than 30% of energy from fat, the odds ratio for having plasma apo B levels above 1.04 g/L for A94 carriers was of 0.40 (p = 0.02) compared to T94/T94 homozygotes. Results were similar for carriers of the A94 allele consuming more than 10% of energy from saturated fat (OR: 0.32, p = 0.005). In conclusion, T94/T94 exhibit higher apo B levels whereas carriers of the A94 allele seem to be protected against high apo B levels when consuming a high fat and saturated fat diet. These findings reinforce the importance to take into account gene-diet interactions in the prevention and management of the metabolic syndrome.

Adult↗

PubMed2004

Sex differences in the relationships of abdominal fat to cardiovascular disease risk among normal-weight white subjects.

The objectives of this study are to investigate the relationships between abdominal fat and risk factors for cardiovascular disease (CVD) among normal-weight (NW) white subjects and to determine how these relationships differ by sex. NW adults (177 males and 258 females) and overweight adults (133 males and 111 females) from the Québec Family Study and the HERITAGE Family Study were retained for this study. Risk factors included systolic and diastolic blood pressures, low-density lipoprotein and high-density lipoprotein cholesterols, triglycerides, and fasting glucose. Only in NW female adults, abdominal visceral fat (AVF) area assessed by computed tomography was significantly correlated with all risk factors, except for fasting glucose, even after age, study cohort, and fat mass were taken into account. NW female subjects with at least one risk factor had a significantly higher AVF than those without risk factors, although the difference was small. Thus, only NW female adults with more AVF tended to have a more adverse CVD risk factor profile.

Abdomen↗

PubMed2003

Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Quebec Family Study.

A genome-wide linkage study was performed to identify chromosomal regions harboring genes influencing lipid and lipoprotein levels. Linkage analyses were conducted for four quantitative lipoprotein/lipid traits, i.e., total cholesterol, triglyceride, HDL-cholesterol (HDL-C), and LDL-C concentrations, in 930 subjects enrolled in the Québec Family Study. A maximum of 534 pairs of siblings from 292 nuclear families were available. Linkage was tested using both allele-sharing and variance-component linkage methods. The strongest evidence of linkage was found on chromosome 12q14.1 at marker D12S334 for HDL-C, with a logarithm of the odds (LOD) score of 4.06. Chromosomal regions harboring quantitative trait loci (QTLs) for LDL-C included 1q43 (LOD = 2.50), 11q23.2 (LOD = 3.22), 15q26.1 (LOD = 3.11), and 19q13.32 (LOD = 3.59). In the case of triglycerides, three markers located on 2p14, 11p13, and 11q24.1 provided suggestive evidence of linkage (LOD > 1.75). Tests for total cholesterol levels yielded significant evidence of linkage at 15q26.1 and 18q22.3 with the allele-sharing linkage method, but the results were nonsignificant with the variance-component method. In conclusion, this genome scan provides evidence for several QTLs influencing lipid and lipoprotein levels. Promising candidate genes were located in the vicinity of the genomic regions showing evidence of linkage.

Adult↗

PubMed2003

The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Québec Family Study.

The metabolic syndrome is a complex disorder characterized by an atherogenic dyslipidemia resulting from the interaction between genetic and nutritional factors. The objective of this study was to examine in a cohort of 720 adults participating in the Québec Family Study (QFS) whether dietary fat interacts with the P12A polymorphism in the gene encoding the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear factor that regulates lipid and glucose homeostasis. Carriers of the A12 allele had a higher body mass index (BMI), waist circumference, fat mass as well as subcutaneous adipose tissue and visceral adipose tissue (VAT) areas both assessed by computed tomography than P12/P12 homozygotes. Total fat and saturated fat intakes estimated from a 3-day food record were significantly correlated with several components of the metabolic syndrome in P12/P12 homozygotes. None of these expected associations were observed among carriers of the A12 allele. Furthermore, in a model including the PPAR-gamma P12A polymorphism, fat intake, age and gender, PPAR-gamma P12A and its interaction with fat intake were associated with BMI and waist circumference. Similar results were obtained when saturated fat intake replaced total fat intake into the model. When the two genotype groups were further classified into quartiles of total fat or saturated fat intake and their characteristics compared, an increase in fat intake was associated with an increase in waist circumference in P12/P12 homozygotes but not in A12 carriers. There was no difference in the waist circumference in carriers of the A12 allele whether the fat or the saturated fat intake was high or low. These results suggest that the PPAR-gamma P12A polymorphism can modulate the association between dietary fat intake and components of the metabolic syndrome.

Adult↗

PubMed2003

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

Changes of heart rate (HR) and blood pressure (BP) relative to baseline levels in response to an extended period of endurance training are indices of cardiovascular adaptability. Familial influences were investigated for HR and BP at work rates of 50 W and 60 % of the maximal oxygen uptake (VO2max) in response to 20 weeks of endurance training. A total of 481 participants from 99 sedentary White nuclear families in the HERITAGE Family Study (HERITAGE) were analyzed using a familial correlation model. Each of these training response phenotypes was adjusted for the effects of age, BMI, cigarette smoking, baseline VO2max, and its baseline values in fathers, mothers, sons and daughters, respectively. We found that maximal heritabilities reached 34 % and 29 % for HR training responses at 50 W and 60 % of VO2 max, respectively. The heritability was 22 % for systolic BP (SBP) training response at 50 W, but negligible at 60 % of VO2max. No significant heritabilities were found for diastolic BP (DBP) training responses at either 50 W or 60 % of VO2max. Familial influences for exercise HR and BP training responses were also assessed in a total of 257 participants from 113 Black family units in HERITAGE. However, there was no significant familial resemblance, which may be attributable to the small sample size. In conclusion, HR and SBP training responses during submaximal exercise in Whites were influenced by a modest, but significant, familial component. These observations are therefore in contrast to substantial familial effects (heritability estimates of about 50 %) previously reported for these variables measured at baseline.

Adaptation, Physiological↗

PubMed2003

Evidence of major genes for exercise heart rate and blood pressure at baseline and in response to 20 weeks of endurance training: the HERITAGE family study.

Major gene effects on exercise heart rate (HR) and blood pressure (BP) measured at 50 W and 80 % maximal oxygen uptake (VO (2)max) were assessed in 99 White families in the HERITAGE Family Study. Exercise HR and BP were measured both before and after 20 weeks of endurance training. The baseline phenotypes were adjusted for the effects of age and BMI, whereas the training responses (post-training minus baseline) were adjusted for the effects of age, BMI and the corresponding baseline values, within four sex-by-generation groups. Baseline exercise HR at 50 W was under the influence of a major recessive gene and a multifactorial component, which accounted for 30 % and 27 % of the variance, respectively. The training response was found to be under the influence of a major dominant gene, which accounted for 27 % of the variance. These significant major gene effects were independent of the effects of cigarette smoking, baseline VO (2)max, and the resting HR levels. No significant interactions were found between genotype and age, sex, or BMI. No major gene effect was found for exercise BP. Instead, we found the baseline exercise BP at 50 W and 80 % VO (2)max and the training response at 50 W were solely influenced by multifactorial effects, which accounted for about 50 %, 40 % and 20 % of the variance, respectively. No familial resemblance was found for training responses in exercise HR or BP at 80 % VO (2)max. Segregation analysis also was carried out for exercise HR in Whites pooled with a small sample of Blacks in HERITAGE. Similar major effects were found, but the transmission from parents to offspring did not follow Mendelian expectations, suggesting sample heterogeneity. In conclusion, submaximal exercise HR at baseline and in response to endurance training was influenced by putative major genes, with no evidence of interactions with sex, age or BMI, in contrast to a multifactorial etiology for exercise BP.

Black People↗

PubMed2002

The hormone-sensitive lipase gene and body composition: the HERITAGE Family Study.

OBJECTIVE: To investigate whether the C-60G polymorphism and other markers in the hormone-sensitive lipase (LIPE) gene are associated with baseline body composition and free-fatty acid (FFA) concentrations measured at rest and during low-intensity exercise in white and black subjects participating in the HERITAGE Family Study. SUBJECTS: Adult sedentary white (245 men and 258 women) and black (91 men and 185 women) subjects. MEASUREMENTS: body mass index (BMI); fat mass (FAT); percentage body fat (%FAT); fat-free mass (FATFR); sum of eight skinfolds (SF8); subcutaneous (ASF), visceral (AVF) and total (ATF) abdominal fat areas assessed by CT scan; plasma FFA concentrations measured at rest (FFAR), at a power output of 50 W (FFA50) and at a relative power output of 60% of VO(2max) (FFA60%); and fasting insulin (INS). STATISTICAL ANALYSIS: Association between the C-60G polymorphism of the LIPE gene and each phenotype was tested separately in men and women using ANCOVA with the effects of age and race as covariates and with further adjustment for FAT for ASF, AVF, ATF, FFAR, FFA50 and FFA60%. Secondly, owing to significant gene-by-race interaction, associations were investigated separately in each of the two race groups. Linkage was tested with the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE gene. RESULTS: There were no race differences in the allele frequencies of the C-60G polymorphism of the LIPE gene. No association or gene-by-race interaction was observed in men. However, in women, strong gene-by-race interactions were observed for BMI (P=0.0005), FAT (P=0.0007), %FAT (P=0.0003), SF8 (P=0.0001), ASF (P=0.03) and ATF (P=0.01). When the analysis was performed separately in each race, white women carriers of the -60G allele exhibited lower %FAT (P=0.005) and SF8 (P=0.01) than non-carriers, while in black women, the -60G allele was associated with higher BMI (P=0.004), FAT (P=0.009), %FAT (P=0.01) and SF8 (P=0.0009). These associations were no longer significant after adjusting for INS. Evidence of linkage was observed in whites with ATF, FFAR, FFA50 and FFA60%. CONCLUSION: These results suggest that the C-60G polymorphism in the LIPE gene plays a role in determining body composition and that its effect is sex-, race- and insulin-dependent.

Abdomen↗

PubMed2002

Is adiposity at normal body weight relevant for cardiovascular disease risk?

OBJECTIVE: To examine the relation between adiposity and risk factors for cardiovascular disease (CVD) in normal weight (NW) individuals. METHODS: Cross-sectional study using the sample of white people, aged from 17 to 60 y from the Québec Family Study and the Heritage Family Study. NW subjects with a body mass index (BMI) between 18.5 and 25 kg/m(2) (181 males and 265 females) and overweight (OW) subjects with a BMI between 25 and 30 kg/m(2) (133 males and 114 females) were retained for this study. NW subjects were divided into quintiles of each adiposity variable, then the quintiles and the OW group were evaluated for the presence of CVD risk factors. Using logistic regression analysis, the odds ratio (OR) for the prevalence of risk factors for each quintile of each adiposity variable and the OW group was estimated relative to the first quintile in NW subjects. Mean values of adiposity variables were compared between the subjects with and without risk factors. In these analyses, age and study cohort effects were taken into account. MEASUREMENTS: Percentage body fat (%fat) and fat mass (FM) measured by underwater weighing were available as adiposity variables. Risk factors included systolic and diastolic blood pressure, LDL and HDL cholesterol, triglycerides and fasting glucose. RESULTS: Wide ranges of values were observed for adiposity variables. HDL cholesterol, triglycerides and fasting glucose in NW males and HDL cholesterol in NW females were significantly correlated with all adiposity variables. For males, higher quintiles of adiposity variables in the NW group and the OW group tended to have higher ORs compared to the first quintiles for the risk factor variables. The fifth quintiles of all adiposity variables had the highest ORs (3.15 for %fat and 3.77 for FM) and they were significantly different from the first quintiles. OW males had ORs similar to those of the fifth quintiles for the risk factor variables. On the other hand, for females, the relatively linear associations were less clear in the NW group. In NW males, the subjects with at least one risk factor had significantly higher %fat and FM than the subjects without risk factors. In NW females, no significant difference was observed for these adiposity variables between the subjects with and without risk factors. CONCLUSION: NW males with elevated adiposity had higher prevalence of risk factors than NW males with less adiposity and the prevalence in the former was rather similar to that seen in OW males. On the other hand, measures of adiposity added little additional information to the BMI classification of NW on CVD risk factors in females.

Adipose Tissue↗

PubMed2002

A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence.

BACKGROUND: The melanocortin system includes five receptors (MC1R to MC5R), and mouse and human MC4R has been shown to be involved in the regulation of feeding, and mouse MC3R in body composition. To verify a possible similar effect of MC3R in humans, we analyzed one insertion and one single nucleotide polymorphism by restriction fragment length polymorphisms (RFLP), and a microsatellite (D20S32e) in relation to body composition and glucose metabolism. METHODS: Eight hundred twelve subjects of the Québec Family Study (QFS) cohort were analyzed for body composition, food intake, and energy metabolism phenotypes. Southern Blot with the complete MC3R cDNA was used to detect a new +2138InsCAGACC variant by Pst1 restriction. PCR-RFLP with BsaJ1 was used to type amino acid polymorphism V81I arising from a G241A nucleotide change. PCR and automatic DNA sequencers were used for the analysis of the TG dinucleotide repeat D20S32e located between -1933/-1892 of MC3R. In a covariance analysis among genotypes, phenotypes were adjusted for age and sex as covariates. Food intake and energy metabolism phenotypes were also adjusted for body mass index (BMI), and leptin and abdominal fat, as assessed by a computed tomography scan, for fatness using six skinfold thicknesses. RESULTS: An association between the +2138InsCAGACC MC3R polymorphism was observed with fat mass (FM), percent body fat (%FAT), and total abdominal fat (ATF). Homozygote subjects for the +2138 insertion variant allele in normal weight (BMI < 25 kg/m(2)) and overweight (25 < or = BMI < 30 kg/m(2)) subjects showed a similar level of fatness despite the overall difference in BMI. In normal weight, homozygotes for the insertion allele showed higher mean values than heterozygotes and homozygotes for wild-type allele without insertion (%FAT: 24.0 +/- 1.1 versus 19.3 +/- 0.9 and 20.5 +/- 0.8, p = 0.0005; FM: 15.7 +/- 0.9 kg versus 11.7 +/- 0.7 kg and 12.6 +/- 0.6 kg, p = 0.0003). In contrast, overweight subjects homozygote for the variant allele showed lower mean values (%FAT: 27.0 +/- 1.2 versus 31.4 +/- 0.8 and 30.9 +/- 0.7, p = 0.002; FM: 18.3 +/- 1.0 kg versus 22.8 +/- 0.8 kg and 22.0 +/- 0.6 kg, p = 0.0001). This resulted in a similar level of body fat between both BMI groups for subjects homozygote for the insertion allele versus wild-type allele carriers (%FAT: +/-2-3% versus +/-10-12%; FM: +/-2 kg versus +/-9-11 kg). In obese subjects (BMI > or = 30 kg/m(2) ), a lower level of ATF was seen (-15%, p = 0.002). Other polymorphisms and phenotypes tested showed no association. CONCLUSION: A new 12138InsCAGACC MC3R polymorphism is associated with the level of adiposity and with body fat partitioning in interaction with corpulence in humans.

Adipose Tissue↗

PubMed2001

Genetic variation at the lipoprotein lipase locus and plasma lipoprotein and insulin levels in the Québec Family Study.

The associations between the S447X, BamHI, HindIII and PvuII DNA variants of the lipoprotein lipase (LPL) gene and indicators of body fat, fat distribution and plasma lipids and insulin were studied in the Québec Family Study cohort. Strong linkage disequilibrium among all the markers was observed. For the S447X polymorphism, plasma very low density lipoprotein (VLDL)-cholesterol (chol) (P<0.001), total triglyceride (TG) (P=0.033) and VLDL-TG (P<0.001) levels were lower and high density lipoprotein (HDL)-chol level higher (P<0.001) in the subjects homozygous or heterozygous for X447 (X447+, n=160) compared to the homozygotes for the S447 allele (X447-, n=576). The BamHI, PvuII and HindIII polymorphisms were not associated with the plasma lipid values when all X447 allele carriers were removed. In addition, the HindIII polymorphism as well as the HindIII and S447X markers combination influenced the insulin area under the curve during an oral glucose tolerance test. We conclude that DNA sequence variation in the LPL gene contributes significantly to the variability in the levels of VLDL-chol, total- and VLDL-TG as well as HDL-chol. The effects of the other polymorphisms considered here are most likely mediated by their linkage disequilibrium with the S447X mutation. In addition, genetic variation at the LPL locus may, by an unknown mechanism, influence insulin metabolism but not body fat variability.

Adult↗