Relationships between the functional PPARα Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people

Sparsø, Thomas; Hussain, Meena S.; Andersen, Gitte; Hainerová, Irena Aldhoon; Borch‐Johnsen, Knut; Jorgensen, Torbert; Hansen, Torben; Pedersen, Oluf

doi:10.1016/j.ymgme.2006.10.007

Cited by 39 publications

(28 citation statements)

References 25 publications

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“…Meanwhile, in Caucasian populations, MAF ranged from .06 to .08. 13,[18][19][20][21] In agreement with our current and previous findings, 7 PPARα L162V SNP was not associated with obesity in the Chinese Han, 17 Brazilians 22 and Caucasians. 4,[23][24][25] Furthermore, a study conducted by Robitaille et al 23 reported no association of this SNP with Met-S among Caucasian men, consistent with our current finding.…”

Section: Discussionsupporting

confidence: 92%

Screening of Peroxisome Proliferator-activated Receptors (PPARs) α, γ and δ Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-ethnic Malaysian Population

Chia¹,

Fan²,

Say

2015

Ethn Dis

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Objective: This study aimed to investigate the association of peroxisome proliferatoractivated receptor (PPAR) genes PPARα L162V, PPARγ2 C161T and PPARδ T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met-S) in a multi-ethnic population in Kampar, Malaysia.Methods: Socio-demographic data, anthropometric and biochemical measurements (plasma lipid profile, adiponectin and interleukin-6 [IL-6] levels) were taken from 307 participants (124 males; 180 obese; 249 Met-S; 97 Malays, 85 ethnic Chinese, 55 ethnic Indians). Results:The overall minor allele frequencies were .08, .22 and .30 for PPAR α L162V, γ C161T, δ T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by χ 2 analysis, ethnicity-stratified and logistic regression analyses. Nevertheless, participants with V162 allele of PPARα had significantly higher IL-6, while those with T161 allele of PPARγ2 had significantly lower HOMA-IR. Conclusions

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Section: Discussionsupporting

confidence: 92%

Screening of Peroxisome Proliferator-activated Receptors (PPARs) α, γ and δ Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-ethnic Malaysian Population

Chia¹,

Fan²,

Say

2015

Ethn Dis

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“…Moreover, hepatic TG content was inversely correlated with serum β-hydroxybutyrate level (Supplemental Figure 15, E-G). Previous studies have shown that the L162V variant of PPARA was significantly associated with several components of the metabolic syndrome, including fasting hypertriglyceridemia (54)(55)(56). We also found that obese subjects with the PPARA L162V genotype had a higher hepatic TG content (Supplemental Figure 16).…”

Section: Methodssupporting

confidence: 70%

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

Lu¹,

Liu²,

Jiao³

et al. 2014

J. Clin. Invest.

114

128

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Periostin neutralizing Ab. The hybridoma cell lines secreting mouse mAb against mouse periostin were generated by Abmart Co., according to the standard hybridoma technique (72). The mouse mAbs were purified by Protein A affinity chromatograph. mAb purity was confirmed by HPLC. The concentrations of the obtained mAbs were measured by Mouse IgG ELISA Quantitation kit (Bethyl Laboratories), following the manufacturer's instructions. The kinetic parameters of the mAbs were determined using a Biacore T100 instrument (Biacore AB). Purified Ab was diluted in saline and injected at a dose of 5 mg/kg into db/db mice for 2 weeks.Statistics. All values are shown as mean ± SEM. Statistical differences were determined by 2-way ANOVA with Bonferroni-adjusted post-test or by 2-tailed Student's t test. A P value less than 0.05 was considered significant.

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“…Type 2 diabetes was defined according to the World Health Organization (19). Obesity was defined as described (20), and dyslipidemia was defined as fasting serum triglycerides Ն1.7 mmol/l or HDL cholesterol Ͻ0.9 mmol/l for men or Ͻ1.0 mmol/l for women and/or current or previous treatment with lipid-lowering drugs (21). Biochemical assays and anthropometrical measurements.…”

Section: Methodsmentioning

confidence: 99%

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

et al. 2008

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OBJECTIVE-The gene encoding the ␣2 Heremans-Schmid glycoprotein (AHSG) is a credible biological and positional candidate gene for type 2 diabetes and the metabolic syndrome, and previous attempts to relate AHSG variation with type 2 diabetes and obesity in Swedish and French Caucasians have been largely successful. We related seven frequent AHSG tag single nucleotide polymorphisms to a range of metabolic traits, including type 2 diabetes, obesity, and dyslipidemia. RESEARCH DESIGN AND METHODS-The polymorphisms were genotyped in 7,683 white Danish subjects using Taqman allelic discrimination or chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, providing a statistical power of Ͼ99% to replicate previous findings. Data were analyzed in case-control and haplotype settings, and quantitative metabolic traits were examined for association. Moreover, epistatic effects between AHSG variants and insulin receptor substrate-1 (IRS1) and ␤-2-adrenergic receptor polymorphisms were investigated.RESULTS-The Ϫ469TϾG (rs2077119) and IVS6ϩ98CϾT (rs2518136) polymorphisms were associated with type 2 diabetes (P ϭ 0.007 and P ϭ 0.006, respectively, or P corr ϭ 0.04 and P corr ϭ 0.03, respectively, following correction for multiple hypothesis testing), and in a combined analysis of the present and a previous study Ϫ469TϾG remained significant (odds ratio 0.90 [95% CI 0.84 -0.97]; P ϭ 0.007). Furthermore, two AHSG haplotypes were associated with dyslipidemia (P ϭ 0.003 and P corr ϭ 0.009). Thr248Met (rs4917) tended to associate with lower fasting and post-oral glucose tolerance test serum insulin release (P ϭ 0.02, P corr ϭ 0.1 for fasting and P ϭ 0.04, P corr ϭ 0.2 for area under the insulin curve) and improved insulin sensitivity estimated by the homeostasis model assessment of insulin resistance (9.0 vs. 8.6 mmol ⅐ l Ϫ1 ⅐ pmol Ϫ1 ⅐ l Ϫ1 ; P ϭ 0.01, P corr ϭ 0.06). Indications of epistatic effects of AHSG variants with the IRS1 Gly971Arg polymorphism were observed for fasting serum triglyceride concentrations.CONCLUSIONS-Based on present and previous findings, common variation in AHSG may contribute to the interindividual variation in metabolic traits. Diabetes 57:1427-1432, 2008 T he ␣ 2 Heremans-Schmid glycoprotein (AHSG) is secreted mainly by the liver and is abundant in plasma. AHSG inhibits insulin-stimulated insulin receptor autophosphorylation, insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS1), and the association of IRS1 with the p85 subunit of phosphatidylinositol-3 kinase in vitro (1-3). Elevated plasma AHSG was associated with insulin resistance in humans (4), and AHSG levels were higher in subjects with impaired glucose tolerance (5) and women with gestational diabetes (6). Ahsg knockout mice demonstrate increased basal and insulin-stimulated insulin receptor phosphorylation, increased glucose clearance, and insulin sensitivity (7). Moreover, even on a high-fat diet and at old age Ahsg knockout mice were resistant to weight gain and remained insulin sens...

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Relationships between the functional PPARα Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people

Cited by 39 publications

References 25 publications

Screening of Peroxisome Proliferator-activated Receptors (PPARs) α, γ and δ Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-ethnic Malaysian Population

Screening of Peroxisome Proliferator-activated Receptors (PPARs) α, γ and δ Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-ethnic Malaysian Population

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

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