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Bossé, Yohan

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Bossé

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Yohan

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Université Laval. Département de médecine moléculaire

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Voici les éléments 1 - 10 sur 19
  • PublicationRestreint
    Heritability of LDL peak particle diameter in the Quebec Family Study
    (Wiley-Liss, Inc., 2003-11-18) Bouchard, Claude; Pérusse, Louis; Lamarche, Benoît; Bossé, Yohan; Rice, Treva; Vohl, Marie-Claude; Rao, D. C. (Dabeeru C.); Després, Jean-Pierre
    LDL size has been associated with the risk of coronary heart disease. The objective of the present study was to verify whether familial factors influence LDL peak particle diameter (LDL‐PPD), a quantitative trait reflecting the size of the major LDL subclass. LDL‐PPD was measured by 2–16% polyacrylamide gradient gel electrophoresis in 681 members of 236 nuclear families participating in the Quebec Family Study. LDL‐PPD was adjusted for age (LDL‐PPD1), age and body mass index (LDL‐PPD2), or age, body mass index, and plasma triglyceride levels (LDL‐PPD3) separately in men and women. The residual scores were used to test for familial aggregation, using an ANOVA and to compute maximum likelihood estimates of familial correlations. The ANOVA test revealed that family lines accounted for 47.4%, 46.7%, and 48.9% of the variance in the LDL‐PPD1, LDL‐PPD2, and LDL‐PPD3 phenotypes, respectively. The pattern of familial correlations revealed no significant spouse correlations but significant parent‐offspring and sibling correlations for the three LDL‐PPD phenotypes, with maximal heritability estimates of 59%, 58%, and 52% for LDL‐PPD1, LDL‐PPD2, and LDL‐PPD3, respectively. These results suggest that LDL‐PPD strongly aggregates in families, and that the familial resemblance appears to be primarily attributable to genetic factors. Genes responsible for this genetic contribution remain to be identified. Genet Epidemiol 25:375–381, 2003. © 2003 Wiley‐Liss, Inc.
  • PublicationAccès libre
    Influences of gestational obesity on associations between genotypes and gene expression levels in offspring following maternal gastrointestinal bypass surgery for obesity.
    (Public Library of Science, 2015-01-20) Guénard, Frédéric; Marceau, Picard; Bossé, Yohan; Lamontagne, Maxime; Cianflone, Katherine M.; Kral, John G.; Vohl, Marie-Claude; Deshaies, Yves
    Maternal obesity and excess gestational weight gain with compromised metabolic fitness predispose offspring to lifelong obesity and its comorbidities. We demonstrated that compared to offspring born before maternal gastrointestinal bypass surgery (BMS) those born after (AMS) were less obese, with less cardiometabolic risk reflected in the expression and methylation of diabetes, immune and inflammatory pathway genes. Here we examine relationships between gestational obesity and offspring gene variations on expression levels. Methods : Whole-genome genotyping and gene expression analyses in blood of 22 BMS and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5-Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we analyzed interactions between offspring gene variations and maternal surgical status on offspring gene expression levels. Altered biological functions and pathways were identified and visualized using DAVID and Ingenuity Pathway Analysis. Results : Significant interactions (p ≤ 1.22x10-12) were found for 525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved. Gene function and pathway analysis demonstrated enrichment of transcription and of cellular metabolism functions and overrepresentation of cellular stress and signaling, immune response, inflammation, growth, proliferation and development pathways. Conclusion : We suggest that impaired maternal gestational metabolic fitness interacts with offspring gene variations modulating gene expression levels, providing potential mechanisms explaining improved cardiometabolic risk profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate metabolism.
  • PublicationAccès libre
    Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Québec Family Study
    (American Society for Biochemistry et Molecular Biology, Inc., 2003-12-16) Bouchard, Claude; Chagnon, Yvon C.; Pérusse, Louis; Rice, Treva; Bossé, Yohan; Rao, D. C. (Dabeeru C.); Vohl, Marie-Claude; Després, Jean-Pierre
    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.
  • PublicationRestreint
    Evidence for a major quantitative trait locus on chromosome 17q21 affecting low-density lipoprotein peak particle diameter
    (Grune & Stratton, 2003-05-05) Bouchard, Claude; Chagnon, Yvon C.; Pérusse, Louis; Lamarche, Benoît; Bossé, Yohan; Rice, Treva; Vohl, Marie-Claude; Rao, D. C. (Dabeeru C.); Després, Jean-Pierre
    Background— Several lines of evidence suggest that small dense LDL particles are associated with the risk of coronary heart disease. Heritability and segregation studies suggest that LDL particle size is characterized by a large genetic contribution and the presence of a putative major genetic locus. However, association and linkage analyses have thus far been inconclusive in identifying the underlying gene(s). Methods and Results— An autosomal genome-wide scan for LDL peak particle diameter (LDL-PPD) was performed in the Québec Family Study. A total of 442 markers were genotyped, with an average intermarker distance of 7.2 cM. LDL-PPD was measured by gradient gel electrophoresis in 681 subjects from 236 nuclear families. Linkage was tested by both sib-pair–based and variance components–based linkage methods. The strongest evidence of linkage was found on chromosome 17q21.33 at marker D17S1301, with an LOD score of 6.76 by the variance-components method for the phenotype adjusted for age, body mass index, and triglyceride levels. Similar results were obtained with the sib-pair method (P<0.0001). Other chromosomal regions harboring markers with highly suggestive evidence of linkage (P≤0.0023; LOD ≥1.75) include 1p31, 2q33.2, 4p15.2, 5q12.3, and 14q31. Several candidate genes are localized under the peak linkages, including apolipoprotein H on chromosome 17q, the apolipoprotein E receptor 2, and members of the phospholipase A2 family on chromosome 1p as well as HMG-CoA reductase on chromosome 5q. Conclusions— This genome-wide scan for LDL-PPD indicates the presence of a major quantitative trait locus located on chromosome 17q and others interesting loci influencing the phenotype.
  • PublicationRestreint
    Combined effects of PPARγ2 P12A and PPARα L162V polymorphisms on glucose and insulin homeostasis : the Québec Family Study
    (Springer-Verlag, 2003-11-20) Bouchard, Claude; Pérusse, Louis; Weisnagel, John; Bossé, Yohan; Vohl, Marie-Claude; Després, Jean-Pierre
    Peroxisome proliferator-activated receptors γ2 and α are nuclear factors known to be important regulators of lipid and glucose metabolism. Two polymorphisms, namely PPARγ2 P12A and PPARα L162V, were investigated for their individual and interaction effects on glucose and insulin homeostasis. Genotypes were determined in 663 nondiabetic adults participating in the Québec Family Study and who underwent an oral glucose tolerance test (OGTT). The insulin and C-peptide areas under the curve (AUC) following the OGTT were higher in subjects carrying the PPARα V162 allele compared to homozygous for the L162 allele. When subjects were grouped according to both polymorphisms, higher levels of insulin and C-peptide during the OGTT were observed for those carrying the PPARα V162 allele except when they carry at the same time the PPARγ2 A12 allele. Thus, the PPARγ2 A12 allele seems protective against the deleterious effect of the PPARα V162 allele. Furthermore, a significant gene-gene interaction was observed for the acute (0–30 min) (p<0.001) and the total (p=0.05) C-peptide AUC following the OGTT. These results provide evidence of a gene-gene interaction in the regulation of plasma glucose-insulin homeostasis, and emphasize that these interactions need to be taken into account when dissecting the genetic etiology of complex disorders.
  • PublicationRestreint
    Influence of the angiotensin-converting enzyme gene insertion/deletion polymorphism on lipoprotein/lipid response to gemfibrozil
    (Blackwell Munksgaard, 2002-07-18) Brochu, Martin.; Bossé, Yohan; Dumont, Martine; Prud'homme, Denis; Vohl, Marie-Claude; Després, Jean-Pierre; Bergeron, Jean
    Evidence suggests that fibrate therapy reduces the risk of recurrent coronary heart disease among men with low levels of high density lipoprotein cholesterol (HDL-C). Indirect observations and new possible biological pathways suggest that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism might modulate the lipoprotein/lipid profile and its response to fibrate therapy. To assess the possible interaction between fibrate therapy and such variants on plasma lipid and lipoprotein levels, 65 dyslipidemic abdominally obese men were treated for 6 months with or without gemfibrozil (600 mg twice daily). No differences in baseline plasma lipid and lipoprotein levels were found between genotype groups except for the HDL(3)-C subfraction, which was higher in the DD group (p = 0.02). A two-way factorial ANOVA was used to evaluate the effect of the genotype (DD homozygotes vs I allele carriers), the treatment (placebo vs gemfibrozil), and the interaction between these two independent variables on changes observed in lipid and lipoprotein concentrations. A significant genotype-by-treatment interaction (p = 0.02) was found for the plasma HDL-C response to the intervention program. In fact, having the DD genotype and being treated with gemfibrozil had a synergical effect on HDL-C levels. The results of this study suggest that the ACE I/D polymorphism influences the effect of gemfibrozil on plasma HDL-C levels.
  • PublicationAccès libre
    Compendium of genome-wide scans of lipid-related phenotypes : adding a new genome-wide search of apolipoproteins levels
    (American Society for Biochemistry and Molecular Biology, 2004-09-16) Bouchard, Claude; Chagnon, Yvon C.; Pérusse, Louis; Rice, Treva; Bossé, Yohan; Rao, D. C.; Vohl, Marie-Claude; Després, Jean-Pierre
    The genetic dissection of complex inherited diseases is a major challenge. Despite limited success in finding genes, substantial data based on genome-wide scan strategies is now available for a variety of diseases and related phenotypes. This can perhaps best be appreciated in the field of lipid and lipoprotein levels, where the amount of information generated is becoming overwhelming. We have created a database containing the results from whole-genome scans of lipid-related phenotypes undertaken to date. The usefulness of this database is demonstrated by performing a new autosomal genomic scan on apolipoprotein B (apoB), LDL-apoB, and apoA-I levels, measured in 679 subjects of 243 nuclear families. Linkage was tested using both allele-sharing and variance-component methods. Only two loci provided support for linkage with both methods: a LDL-apoB locus on 18q21.32 and an apoA-I locus on 3p25.2. Adding those findings to the database highlighted the fact that the former is reported as a lipid-related locus for the first time, whereas the latter has been observed before. However, concerns arise when displaying all data on the same map, because a large portion of the genome is now covered with loci supported by at least suggestive evidence of linkage.
  • PublicationRestreint
    Effect of liver FABP T94A missense mutation on plasma lipoprotein responsiveness to a treatment with fenofibrate
    (Springer, 2004-08-01) Brouillette, Charles; Pérusse, Louis; Gaudet, Daniel; Bossé, Yohan; Vohl, Marie-Claude
    Fenofibrate, a peroxisome proliferated activated receptor alpha (PPARa) agonist, has been shown to decrease plasma triglyceride (TG) and increase plasma highdensity lipoprotein (HDL) cholesterol levels despite a large interindividual variation in the response. Fenofibrate-activated PPARa binds to a DNA sequence element termed PPAR response element (PPRE) present in regulatory regions of target genes. A PPRE has been identified in the proximal 5¢ flanking region of the gene encoding the liver fatty acid binding protein (LFABP). LFABP is a small cytosolic protein of 14 kDa present in the liver and the intestine and is a member of the superfamily of the fatty acid binding proteins (FABPs). FABPs play a role in the solubilization of long-chain fatty acids (LCFAs) and their CoA-ester to various intracellular organelles. FABPs serves as intracellular acceptors of LCFAs, and they may also have an impact in ligand-dependent transactivation of PPARs in trafficking LCFAs to the nucleus. Since PPARs are known to regulate the transcription of many genes involved in lipid metabolism, the importance of LFABP in fatty acid uptake has to be considered. The aim of this study was to verify whether genetic variations in the LFABP gene may impact on plasma lipoprotein/lipid levels in the fasting state as well as on the response to a lipid-lowering therapy with fenofibrate on plasma lipids and obesity variables. We also wanted to verify whether the presence of the PPARa L162V mutation interacts with genetic variants in LFABP gene. To achieve this goal, we first determined the genomic structure of the human LFABP gene and then designed intronic primers to sequence the coding regions, all exon-intron splicing boundaries, and the promoter region of the gene in 24 patients showing divergent plasma lipoprotein/lipid response to fenofibrate. Sequence analysis revealed the presence of a T94A missense mutation in exon 3. Interspecies comparison revealed that threonine 94 is conserved among species. We subsequently screened another sample of 130 French Canadian subjects treated with fenofibrate for the presence of the LFABP T94A mutation. Carriers of the A94 allele were at increased risk to exhibit plasma TG levels above 2.00 mmol/l after treatment with fenofibrate [2.75 (1.03–7.34); OR 95% confidence interval (CI)]. In addition, carriers of the A94 allele were characterized by higher baseline plasma-free fatty acid levels (FFA) (p=0.01) and by a lower body mass index (BMI) (p=0.05) and waist circumference (p=0.005) than T94 homozygotes. Moreover, PPARa L162V and LFABP T94A showed to have a synergistic effect on BMI (p interaction = 0.03). These results suggest that the LFABP T94A missense mutation could influence obesity indices as well as the risk to exhibit residual hypertriglyceridmia following a lipid-lowering therapy with fenofibrate.
  • PublicationRestreint
    The peroxisome proliferator-activated receptor alpha Leu162Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in healthy men
    (Oxford University Press, 2005-02-01) Paradis, Ann-Marie; Fontaine-Bisson, Bénédicte; Lamarche, Benoît; Lemieux, Simone; Bossé, Yohan; Vohl, Marie-Claude; Couture, Patrick; Robitaille, Julie; Jacques, Hélène; Tchernof, André
    Background : Serum lipid responses to dietary modification are partly determined by genetic factors. Objective : We tested whether plasma lipoprotein and lipid responsiveness to a modification in the dietary ratio of polyunsaturated to saturated fatty acids (P:S) is influenced by the peroxisome proliferator-activated receptor α (PPARα) Leu162Val polymorphism in healthy men. Design : Ten carriers of the V162 allele and 10 L162 homozygotes were matched according to age and body mass index (BMI). During the protocol, all subjects followed the National Cholesterol Education Program Step I diet, but intake of saturated and polyunsaturated fatty acids was adjusted to obtain a P:S of 0.3 for the first 4-wk period (low-P:S diet) and a P:S of 1.0 for the next 4-wk period (high-P:S diet). Results : At screening, the PPARα Leu162Val polymorphism was not associated with anthropometric indexes or plasma lipoprotein and lipid concentrations. After the high-P:S diet, a significant gene-by-diet interaction was observed for changes in plasma total cholesterol, apolipoprotein (apo) A-I, and cholesterol concentrations in small LDL particles (P ≤ 0.05). Mean differences after the high-P:S diet were observed between genotype groups for plasma apo A-I concentrations (P < 0.05). Changes in BMI, waist circumference, and concentrations of triacylglycerol, phospholipid, and apo B did not differ significantly between groups. Conclusion : The PPARα Leu162Val polymorphism may contribute to interindividual variability in plasma lipoprotein and lipid response after modification of the dietary P:S ratio.
  • PublicationRestreint
    Detection of a major gene effect for LDL peak particle diameter and association with apolipoprotein H gene haplotype
    (Elsevier, 2005-03-08) Bouchard, Claude; Feitosa, Mary F.; Pérusse, Louis; Lamarche, Benoît; Bossé, Yohan; Rice, Treva; Vohl, Marie-Claude; Rao, D. C. (Dabeeru C.); Després, Jean-Pierre
    Low-density lipoprotein (LDL) size, a coronary heart disease risk factor, is influenced by both genetic and environmental factors. Results from the Quebec Family Study (QFS) revealed that the LDL peak particle diameter (LDL-PPD) aggregates in families with a heritability coefficient above 50% and is affected by a major quantitative trait locus on chromosome 17q (LOD=6.8). Complex segregation analyses have consistently demonstrated a major gene effect influencing LDL size. In the present study, we report a similar analysis in the QFS cohort, which suggests that a major gene explains 23% of the variance in age-body mass index and triglyceride-adjusted LDL-PPD. The most intuitive positional candidate gene on chromosome 17q is the apolipoprotein H gene. Direct sequencing of the promoter, coding regions, and exon-intron splicing boundaries of this gene revealed the presence of three missense mutations and two polymorphisms in the untranslated regions. Using family-based association tests, none of these variants was individually associated with LDL-PPD. However, analysis of the haplotypes constructed from the three missense mutations, suggested that one particular haplotype (frequency=20.9%) was associated with a significant increase in LDL-PPD trait values (p=0.046). Taken together, these results suggest the presence of a major gene effect influencing LDL-PPD and a positive association with a positional candidate gene located on chromosome 17q. Replication of the association between apolipoprotein H gene haplotype and LDL-PPD is required before reaching firm conclusion.