Dataset Information

Association of peroxisome proliferator-activated receptor ?/?/? with obesity, and gene-gene interaction, in the Chinese Han population.

ABSTRACT: BACKGROUND:We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARs) with obesity and the additional role of gene-gene interaction. METHODS:Participants were recruited within the framework of the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort population survey of an urban community in China. In total, 820 subjects (513 nonobese adults, 307 obese adults) were randomly selected, and no individuals were consanguineous. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped and analyzed. RESULTS:After covariate adjustment, minor alleles of rs2016520 in PPAR? and rs10865170 in PPAR? were associated with lower BMI (P < 0.01 for all). Generalized multifactor dimensionality reduction analysis showed significant gene-gene interaction among rs2016520, rs9794, and rs10865170 in 3-dimensional models (P = 0.0010); prediction accuracy was 0.6011 and cross-validation consistency was 9/10. It also showed significant gene-gene interaction between rs2016520 and rs10865170 in all 2-dimensional models (P = 0.0010); prediction accuracy was 0.6072 and cross-validation consistency was 9/10. CONCLUSIONS:rs2016520 and rs10865170 were associated with lower obesity risk. In addition, interaction was identified among rs2016520, rs9794, and rs10865170 in obesity.

SUBMITTER: Luo W

PROVIDER: S-EPMC3700259 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Association of peroxisome proliferator-activated receptor α/δ/γ with obesity, and gene-gene interaction, in the Chinese Han population.

Luo Wenshu W Guo Zhirong Z Wu Ming M Hao Chao C Hu Xiaoshu X Zhou Zhengyuan Z Zhou Zhiwu Z Yao Xingjuan X Zhang Lijun L Liu Jingchao J

Journal of epidemiology 20130401 3

<h4>Background</h4>We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARs) with obesity and the additional role of gene-gene interaction.<h4>Methods</h4>Participants were recruited within the framework of the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort population survey of an urban community in China. In total, 820 subjects (513 nonobese adults, 307 obese adults) were randomly selecte ...[more]

PMID: 23545576

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Project description:Peroxisome proliferator-activated receptors (PPARs) have unique functions in energy metabolism regulation but are also involved in regulation of the inflammatory process and obesity. The aim of this study was to analyse potential associations between polymorphisms of PPARA (rs1800206), PPARD (rs1053049; rs2267668) and PPARG (rs1801282) and overweight parameters. One hundred and sixty-six males, unrelated Caucasian military professionals, were recruited in the genetic case-control study conducted in the period 2016-2019. All the participants were aged 21-41 and had similar levels of physical activity. Body mass, height and body composition were measured. The participants were divided into two groups depending on their BMI (body mass index) and FMI (fat mass index). The control group consisted of people with BMI between 20.0 and 25.0 or FMI values ≤ 6, while the overweight group consisted of people with BMI of ≥ 25.0 or FMI values > 6. Genomic DNA was isolated from extracted buccal cells. All samples were genotyped using real-time polymerase chain reaction (real-time PCR). It was found that two polymorphisms rs2267668 and rs1053049 of the PPARD gene were significantly associated with BMI: SNP rs2267668 for the dominant (OR = 2.04, 95%CI 1.01-4.11, p-value = 0.04) model (A/G-G/G vs A/A). The likelihood of being overweight was over 2 times smaller for allele A. A relationship between the polymorphism of PPARG (rs1801282) and BMI was found for the overdominant (OR = 2.03, 95%CI 1.03-4.00, p-value = 0.04) model (C/G vs C/C-G/G). Significant associations were found in different models for PPARD, PPARG and PPARA genes with BMI. In SNP rs2267668 for the codominant genetic model (G/G vs A/A) (p-value = 0.04) and in SNP rs1053049 for the codominant (C/C vs T/T) (p-value = 0.01) and the recessive genetic model (C/C vs T/T-C/T) (p-value = 0.004) all polymorphisms were associated with BMI. In conclusion, it was found that three of the four polymorphisms (rs1053049, rs2267668, rs1801282) selected are associated with the risk of being overweight. Having said that, one has to bear in mind that DNA variants do not fully explain the reasons for being overweight. Therefore more research is needed to make a thorough assessment using the latest genomic methods in sequencing and genotyping, combined with epigenomics, proteomics, transcriptomics, and metabolomics.

Project description:BackgroundAtopic dermatitis (AD) is a chronic inflammatory dermatosis now increasingly linked to mutations that alter the structure and function of the stratum corneum. Activators of peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta, and gamma and liver X receptor (LXR) regulate epidermal protein and lipid production, leading to superior barrier function. Additionally, some of these activators exhibit potent antihyperplastic and anti-inflammatory activity in irritant contact dermatitis and acute allergic contact dermatitis murine models.ObjectiveWe evaluated the efficacy of PPAR/LXR activation in a hapten (oxazolone [Ox])-induced AD-like model (Ox-AD) in hairless mice.MethodsOx-AD was established with 10 Ox challenges (every other day) on the flank. After the establishment of Ox-AD, twice-daily topical application with individual PPAR/LXR activators was then performed for 4 days, with continued Ox challenges every other day. The efficacy of topical PPAR/LXR activators to reduce parameters of Ox-AD was assessed physiologically, morphologically, and immunologically.ResultsCertain topical activators of PPARalpha, PPARbeta/delta, and LXR, but not activators of PPARgamma, reversed the clinical dermatosis, significantly improved barrier function, and increased stratum corneum hydration in Ox-AD mice. In addition, the same activators, but again not PPARgamma, largely reversed the immunologic abnormalities in Ox-AD mice, including the increased T(H)2 markers, such as tissue eosinophil/mast cell density, serum thymus and activation-related chemokine levels, the density of chemoattractant receptor-homologous molecule expressed on T(H)2-positive lymphocytes (but not serum IgE levels), and reduced IL-1alpha and TNF-alpha activation, despite ongoing hapten challenges.ConclusionThese results suggest that topical applications of certain activators/ligands of PPARalpha, PPARbeta/delta, and LXR could be useful for the treatment of AD in human subjects.

Dataset Information

Association of peroxisome proliferator-activated receptor ?/?/? with obesity, and gene-gene interaction, in the Chinese Han population.

Publications

Association of peroxisome proliferator-activated receptor α/δ/γ with obesity, and gene-gene interaction, in the Chinese Han population.

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