Dataset Information

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

ABSTRACT: 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.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.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.Our results suggest that some alleles of UCP3 are involved in the etiology of human obesity.

SUBMITTER: Lanouette CM

PROVIDER: S-EPMC1950055 | biostudies-other | 2001 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Lanouette C M CM Giacobino J P JP Pérusse L L Lacaille M M Yvon C C Chagnon M M Kuhne F F Bouchard C C Muzzin P P Chagnon Y C YC

Molecular medicine (Cambridge, Mass.) 20010701 7

<h4>Background</h4>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.<h4>Materials and methods</h4>We analyzed, among 734 subjects from the Québec Family Study, a new GA repeat microsatellite located in intervening se ...[more]

PMID: 11683368

Similar Datasets

Project description:Background and aims: Obesity is a major health problem worldwide. Given the heterogeneous obesity phenotype, an optimal obesity stratification would improve clinical management. Since obesity has a strong genetic component, we aimed to develop a polygenic risk score (PRS) to stratify obesity according to the genetic background of the individuals. Methods: A total of 231 single nucleotide polymorphisms (SNP) significantly associated to body mass index (BMI) from 21 genome-wide association studies were genotyped or imputed in 881 subjects from the Quebec Family Study (QFS). The population was randomly split into discovery (80%; n = 704) and validation (20%; n = 177) samples with similar obesity (BMI ≥ 30) prevalence (27.8% and 28.2%, respectively). Family-based associations with obesity were tested for every SNP in the discovery sample and a weighed and continuous PRS231 was constructed. Generalized linear mixed effects models were used to test the association of PRS231 with obesity in the QFS discovery sample and validated in the QFS replication sample. Furthermore, the Fatty Acid Sensor (FAS) Study (n = 141; 27.7% obesity prevalence) was used as an independent sample to replicate the results. Results: The linear trend test demonstrated a significant association of PRS231 with obesity in the QFS discovery sample (ORtrend = 1.19 [95% CI, 1.14-1.24]; P = 2.0x10-16). We also found that the obesity prevalence was significantly greater in the higher PRS231 quintiles compared to the lowest quintile. Significant and consistent results were obtained in the QFS validation sample for both the linear trend test (ORtrend = 1.16 [95% CI, 1.07-1.26]; P = 6.7x10-4), and obesity prevalence across quintiles. These results were partially replicated in the FAS sample (ORtrend = 1.12 [95% CI, 1.02-1.24]; P = 2.2x10-2). PRS231 explained 7.5%, 3.2%, and 1.2% of BMI variance in QFS discovery, QFS validation, and FAS samples, respectively. Conclusions: These results revealed that genetic background in the form of a 231 BMI-associated PRS has a significant impact on obesity, but a limited potential to accurately stratify it. Further studies are encouraged on larger populations.

Project description:BackgroundSex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex.MethodsA total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models.ResultsWe found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape.ConclusionsThere was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.

Project description:Background & purposeObesity and metabolic disorders were associated with increased risk of MM, a disease characterized by high risk of relapsing and require frequent hospitalizations. In this study, we conducted a retrospective cohort study to explore the association of metabolic obesity phenotypes with the readmission risk of MM.Patients & methodsWe analyzed 34,852 patients diagnosed with MM from the Nationwide Readmissions Database (NRD), a nationally representative database from US. Hospitalization diagnosis of patients were obtained using ICD-10 diagnosis codes. According to obesity and metabolic status, the population was divided into four phenotypes: metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). The patients with different phenotypes were observed for hospital readmission at days 30-day, 60-day, 90-day and 180-day. Multivariate cox regression model was used to estimate the relationship between obesity metabolic phenotypes and readmissions risk.ResultsThere were 5,400 (15.5%), 7,255 (22.4%), 8,025 (27.0%) and 7,839 (35.6%) unplanned readmissions within 30-day, 60-day, 90-day and 180-day follow-up, respectively. For 90-day and 180-day follow-up, compared with patients with the MHNO phenotype, those with metabolic unhealthy phenotypes MUNO (90-day: P = 0.004; 180-day: P = < 0.001) and MUO (90-day: P = 0.049; 180-day: P = 0.004) showed higher risk of readmission, while patients with only obesity phenotypes MHO (90-day: P = 0.170; 180-day: P = 0.090) experienced no higher risk. However, similar associations were not observed for 30-day and 60-day. Further analysis in 90-day follow-up revealed that, readmission risk elevated with the increase of the combined factor numbers, with aHR of 1.068 (CI: 1.002-1.137, P = 0.043, with one metabolic risk factor), 1.109 (CI: 1.038-1.184, P = 0.002, with two metabolic risk factors) and 1.125 (95% CI: 1.04-1.216, P = 0.003, with three metabolic risk factors), respectively.ConclusionMetabolic disorders, rather than obesity, were independently associated with higher readmission risk in patients with MM, whereas the risk elevated with the increase of the number of combined metabolic factors. However, the effect of metabolic disorders on MM readmission seems to be time-dependent. For MM patient combined with metabolic disorders, more attention should be paid to advance directives to reduce readmission rate and hospitalization burden.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets