173 research outputs found
The T111I mutation in the EL gene modulates the impact of dietary fat on the HDL profile in women
No full textThe objective of the present study was to examine the impact of the T111I missense mutation in exon 3 of the endothelial lipase (EL) gene on HDL and its potential interaction effect with dietary fat. The study sample included 281 women and 216 men aged between 17 and 76 years from the Québec Family Study. Plasma HDL3-C levels of I111I homozygote women were higher compared with those of women carrying the wild-type allele (P 0.03). These differences were not attenuated when adjusted for levels of obesity and were not observed among men. Dietary PUFA interacted with the T111I mutation to modulate apolipoprotein A-I (apoA-I) and HDL3-C levels among women. Specifically, a diet rich in PUFA was associated with increased apoA-I levels among women carriers of the I111 allele and with decreased apoA-I among women homozygotes for the wild-type allele (P 0.002). A similar interaction was observed with plasma HDL3-C levels (P 0.003). These interactions were not observed among men. In conclusion, the EL T111I mutation appears to have a modest effect on plasma HDL levels. The gene-diet interaction among women, however, suggests that the T111I missense mutation may confer protection against the lowering effect of a high dietary PUFA intake on plasma apoA-I and HDL3-C levels.—Paradis, M-E., P. Couture, Y. Bossé, J-P. Després, L. Pérusse, C. Bouchard, M-C. Vohl, and B. Lamarche. The T111I mutation in the EL gene modulates the impact of dietary fat on the HDL profile in women
Unearthing Defendants in Toxic Waste Litigation: Problems of Liability and Identification
No full textThis Comment examines two significant barriers to obtaining compensation from waste generators posed by traditional proof requirements, and proposes possible approaches for alleviating them. The author evaluates the plausibility of integrating strict products liability and risk share liability, an adaptation of market share liability, into a unified approach that may provide tort victims with greater access to legal remedies. The author suggests that the court adopt a more progressive analytical framework that is analogous to the theory articulated in Sindell v. Abbott Laboratories, and argues for an allocation of liability based on the relative risk share of generators in a toxic waste disposal market, comprised of an aggregate threat of harm to a plaintiff created by a dumpsite
C polymorphism and dietary fat in French-Canadians
No full textObjective:
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 (PC 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)
Adipose methylome integrative-omic analyses reveal genetic and dietary metabolic health drivers and insulin resistance classifiers
No full textBackground: There is considerable evidence for the importance of the DNA methylome in metabolic health, for example, a robust methylation signature has been associated with body mass index (BMI). However, visceral fat (VF) mass accumulation is a greater risk factor for metabolic disease than BMI alone. In this study, we dissect the subcutaneous adipose tissue (SAT) methylome signature relevant to metabolic health by focusing on VF as the major risk factor of metabolic disease. We integrate results with genetic, blood methylation, SAT gene expression, blood metabolomic, dietary intake and metabolic phenotype data to assess and quantify genetic and environmental drivers of the identified signals, as well as their potential functional roles. Methods: Epigenome-wide association analyses were carried out to determine visceral fat mass-associated differentially methylated positions (VF-DMPs) in SAT samples from 538 TwinsUK participants. Validation and replication were performed in 333 individuals from 3 independent cohorts. To assess functional impacts of the VF-DMPs, the association between VF and gene expression was determined at the genes annotated to the VF-DMPs and an association analysis was carried out to determine whether methylation at the VF-DMPs is associated with gene expression. Further epigenetic analyses were carried out to compare methylation levels at the VF-DMPs as the response variables and a range of different metabolic health phenotypes including android:gynoid fat ratio (AGR), lipids, blood metabolomic profiles, insulin resistance, T2D and dietary intake variables. The results from all analyses were integrated to identify signals that exhibit altered SAT function and have strong relevance to metabolic health. Results: We identified 1181 CpG positions in 788 genes to be differentially methylated with VF (VF-DMPs) with significant enrichment in the insulin signalling pathway. Follow-up cross-omic analysis of VF-DMPs integrating genetics, gene expression, metabolomics, diet, and metabolic traits highlighted VF-DMPs located in 9 genes with strong relevance to metabolic disease mechanisms, with replication of signals in FASN, SREBF1, TAGLN2, PC and CFAP410. PC methylation showed evidence for mediating effects of diet on VF. FASN DNA methylation exhibited putative causal effects on VF that were also strongly associated with insulin resistance and methylation levels in FASN better classified insulin resistance (AUC=0.91) than BMI or VF alone. Conclusions: Our findings help characterise the adiposity-associated methylation signature of SAT, with insights for metabolic disease risk
The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts
No full textA SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples
Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes
No full textDysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR) is a master regulator of fatty acid catabolism, and PPAR activators delay the onset of type 2 diabetes. We examined association between three PPAR gene polymorphisms (an AC variant in intron 1, the L162V variant, and the intron 7 GC variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPAR gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 AC (P < 0.001) and intron 7 GC (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPAR haplotype signficantly influenced age at diagnosis (P = 0.027), with the C-L-C and C-V-C haplotypes (intron 1-L162V-intron 7) accelerating onset of diabetes by 5.9 (P = 0.02) and 10 (P = 0.03) years, respectively, as compared with the common A-L-G haplotype, and was associated with an odds ratio for early-onset diabetes (age at diagnosis 45 years) of 3.75 (95% CI 1.65–8.56, P = 0.002). Intron 1 C-allele carriers also progressed more rapidly to insulin monotherapy (AA 9.4 ± 1.5 and AC + CC 5.3 ± 1.1 years, P = 0.002). These data indicate that PPAR gene variation influences the onset and progression of type 2 diabetes
Amyloid-beta peptide, oxidative stress and inflammation in Alzheimer’s disease: Potential neuroprotective effects of omega-3 polyunsaturated fatty acids
No full textAlzheimer’s disease is the most common form of dementia in the elderly and is a progressive neurodegenerative disorder
characterised by a decline in cognitive function and also profound alterations in mood and behaviour. The pathology of the
disease is characterised by the presence of extracellular amyloid peptide deposits and intracellular neurofibrillary tangles in the
brain. Although many hypotheses have been put forward for the aetiology of the disease, increased inflammation and oxidative
stress appear key to be features contributing to the pathology. The omega-3 polyunsaturated fats, eicosapentaenoic acid (EPA), and
docosahexaenoic acid (DHA) have well-characterised e
ff
ects on inflammation and may have neuroprotective e
ff
ects in a number
of neurodegenerative conditions including Alzheimer’s disease. The aims of this paper are to review the neuroprotective e
ff
ects of
EPA and DHA in Alzheimer’s disease, with special emphasis on their role in modulating oxidative stress and inflammation and
also examine their potential as therapeutic agent
Haplotypes in the phospholipid transfer protein gene are associated with obesity-related phenotypes: the Québec Family Study
No full textBACKGROUND :
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≥30 kg/m2), 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
Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study
No full textThe arcOGEN Consortium should be listed as an author of this article. They contributed to the genome-wide association study results presented in this work. They should be listed in the author byline at position 292 and affiliated with The Arthritis Research UK Osteoarthritis Genetics Consortium. They should also be included in the footnote designating consortia which is underneath the author affiliation list in the PDF version of the article, and in the S2 Text. Please view the correct S2 Text below, containing correct consortia members
Associations between dietary patterns and obesity phenotypes
No full textObjective: To examine whether dietary patterns are associated with obesity phenotypes.
Design: Cross-sectional study.
Subjects: We recruited 664 participants aged between 18 and 55 years. Dietary data were collected from a food frequency questionnaire. A factor analysis was performed to derive dietary patterns. Body mass index (BMI), weight and waist girth were recorded using standard procedures. Fat mass and fat-free mass were assessed by electrical bioimpedance. Obesity was defined as having a BMIX30 kg m2 and a positive FHO (FHO þ ) as having at least one obese first-degree relative.
Results: Two dietary patterns were identified; Western and Prudent. The Western pattern was mainly characterized by a higher consumption of refined grains, French fries, red meats, condiments, processed meats and regular soft drinks whereas the Prudent pattern was mainly characterized by a higher consumption of non-hydrogenated fat, vegetables, eggs and fish and seafood. Subjects in the top tertile of the Western pattern had higher BMI, weight, waist girth, waist-to-hip ratio and fat mass than those in the lower tertile. In contrast, subjects in the top tertile of the Prudent pattern had lower BMI, weight, waist girth, fat mass, HDL-cholesterol levels, and lower triglyceride levels than those in the lowest tertile. Individuals in the upper tertile of the Western pattern were more likely to be obese (obesity was defined as having a BMIX30 kg m2) (OR ¼ 1.82, 95% CI 1.16–2.87) whereas those in the upper tertile of the Prudent pattern were less likely to be obese (OR ¼ 0.62, 95% CI 0.40–0.96). These latter significant associations were only observed among those with FHO þ . No such association was observed among FHO individuals.
Conclusion: Individuals having a high score of Western pattern were more likely to be obese and those having a high score of the Prudent pattern were less likely to be obese, and this is particularly among individuals with an FHO+
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