Effects of Two Common Polymorphisms of Peroxisome Proliferator-Activated Receptor-γ Gene on Metabolic Syndrome

Rhee, Eun-Jung; Oh, Ki Won; Lee, Won Young; Kim, Se Yeon; Oh, Eunhye; Baek, Ki Hyun; Kang, Moo Il; Kim, Sun Woo

doi:10.1016/j.arcmed.2005.04.008

Cited by 70 publications

(52 citation statements)

References 46 publications

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“…We found no relationship between the Pro12Ala, 1431C>T, and -681C>G polymorphisms and the MetS. Thus far, few studies have found an association of PPARG variants with an increased risk for MetS (21,32), while others, in line with our results, revealed no significant associations (15)(16)(17)33). Nevertheless, a large cohort study among nondiabetic Danish subjects found a decreased risk of insulin resistance syndrome associated with the Ala/Ala genotype (34).…”

Section: Discussionsupporting

confidence: 75%

Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

Dujić¹,

Bego²,

Mlinar³

et al. 2014

Journal of Medical Biochemistry

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SummaryBackground: Peroxisome proliferator-activated receptor gamma (PPARg) is a key transcription factor in adipogenesis, and also regulates a number of genes associated with lipid storage and insulin sensitivity. Single nucleotide polymorphisms (SNPs) in the PPARG gene have been associated with obesity and diabetes. In this study, we explored the relationship of three PPARG gene variants with the metabolic syndrome (MetS) and related traits in a population from Bosnia and Herzegovina. Methods: Anthropometric and biochemical parameters were measured in 43 patients with MetS and 43 healthy controls. Subjects were genotyped for Pro12Ala (rs1801282) and 1431C>T (rs3856806) SNPs by classic PCR-restriction fragment length polymorphism analysis, and for -681C>G (rs10865710) variant by real-time PCR. Results: The genotype distributions for the three polymorphisms were not significantly different between MetS patients and controls. The Pro12Ala and 1431C>T variants were associated with lower body mass index in the control subjects (p=0.012 and p=0.049, respectively). In this group, the carriers of Pro12Ala had also lower waist circumference compared to the wild-type homozygotes (p=0.045).

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Section: Discussionsupporting

confidence: 75%

Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

Dujić¹,

Bego²,

Mlinar³

et al. 2014

Journal of Medical Biochemistry

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“…Although a C to T substitution at nucleotide 1431 in exon 6 is a synonymous polymorphism that encodes histidine with either allele, biological relevance is suggested by the results of epidemiological studies showing an association of this polymorphism with metabolic diseases such as type 2 diabetes and atherosclerosis (48). It is proposed that this substitution may modulate expression of PPARÁ by altering mRNA processing or translation, however, no significant associations were found for this polymorphism with cancer risk in this meta-analysis.…”

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confidence: 41%

PPARγ polymorphisms and cancer risk: A meta-analysis involving 32,138 subjects

Wu¹

2010

Oncol Rep

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Abstract. The peroxisome proliferator-activated receptor Á (PPARÁ) has been suggested to act as a tumor suppressor gene. Two common variations of PPARÁ, P12A (Pro12Ala, rs1801282) and C161T (His447His, rs3856806), are thought to have an effect on susceptibility to various carcinomas but the results are inconsistent. In this meta-analysis, we assessed published studies of the association between two common PPARÁ polymorphisms and cancer risk from 26 studies with 27,677 subjects for PPARÁ P12A, from 4 studies with 4,461 subjects for C161T. No significant associations were found in carriers of the rare Ala allele of the P12A polymorphism versus the common Pro/Pro genotype among the studies. In the subgroup analyses by cancer types, carriers of the Ala variant of P12A polymorphism were associated with protection from colorectal cancer (OR=0.84, 95% CI=0.72-0.98, P heterogeneity = 0.014), but the inverse association was found in gastric cancer (OR=2.31, 95% CI=1.59-3.36, P heterogeneity = 0.941). In the stratified analysis by ethnicity, no significant risks were found among Asians, Americans and Caucasians. For PPARÁ C161T, no significant associations were found in any of the studies (OR=1.08, 95% CI=0.95-1.23, P heterogeneity = 0.430) or subgroups. This meta-analysis suggests that the Ala allele of the PPARÁ P12A polymorphism might be a protective factor for colorectal cancer, but a risk factor for gastric cancer. The PPARÁ C161T is marginally associated with cancer susceptibility.

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“…A small study involving 253 Korean women diagnosed with MetS (also defined by NCEP/ATPIII recommendations) did not find any association of this syndrome with the genotypes ana lyzed. There were also no differences between BMI, blood pressure, fasting glucose levels, fasting insulin levels and insulin resistance defined by the homeostatic model assessment in Ala carriers when compared with dominant Pro allele (15).…”

Section: Discussionmentioning

confidence: 90%

Prevalence of the rs1801282 single nucleotide polymorphism of the PPARG gene in patients with metabolic syndrome

Rocha

Barra

Rosa

et al. 2015

Arch. Endocrinol. Metab.

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Objective: This study aimed to get the genotypic and allelic frequencies of rs1801282 in 179 volunteer donors and 154 patients with Metabolic syndrome (MetS) in Brasilia, Brazil and also examine the association with anthropometric, biochemical and hemodynamic variables in the latter group. MetS comprises a group of diseases resulting from insulin resistance, in-creased risk of type 2 diabetes and atherosclerotic cardiovascular disease. MetS is defined by the presence of increased visceral fat, atherogenic dyslipidemia (elevated triglycerides (TGL)), with decreased high density lipoprotein (HDL) and increased low density lipoprotein (LDL) levels, hypertension (BPH) and disturbances in glucose homeostasis representing a significant burden across the world due to the alarming increase in the incidence over the last decades besides their significant morbidity and mortality. Peroxisome proliferator activated receptor-gamma (PPARg) has been mentioned as a candidate gene for determining the risk of MetS. It is a member of the nuclear receptors superfamily and a ligand-activated transcription factor, which regulates the expression of genes involved in the network lipogenesis and adipogenesis, insulin sensitivity, energy balance, inflammation, angiogenesis and atherosclerosis. Among the PPARG genetic variants, single nucleotide polymorphism rs1801282 has been the most extensively studied one since it was first described by Yen and cols. in 1997. This polymorphism is characterized by the replacement of a proline (CCC) to an alanine (GCA) at codon 12 of exon B, due to the exchange of a cytosine with a guanine. The Ala allele frequency varies in different ethnic groups. Materials and methods: DNA was extracted using Chelex-100 method and determinations of genotypes were performed by allele-specific chain reaction. Results: The distribution of genotype frequency of the MetS group was not statistically different from the frequency in the donor population at large. In the first group, genotype frequency was CC to 0.869 and 0.103 for CG, while allelic frequencies were 0.948 for C and 0.052 for G allele. In the group of donors, the genotype and allele frequencies were 0.882 for CC, 0.117 to CG; and 0.941 to 0.059 for G and C, respectively. GG genotype was not found in any of the two groups. The genotype distribution and allele frequencies were in Hardy-Weinberg equilibrium. No marker could be detected from the analysis of anthropometric, biochemical and hemodynamic variables in the MetS group. Conclusion: Our data suggest that this polymorphism is not correlated with predisposition to MetS. The results obtained on a small sample of the population of Brasilia, corroborate the data reported in the literature on the prevalence of this polymorphism in PPAR in populations of different ethnic origins. Arch Endocrinol Metab. 2015;59(4):297-302

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Effects of Two Common Polymorphisms of Peroxisome Proliferator-Activated Receptor-γ Gene on Metabolic Syndrome

Cited by 70 publications

References 46 publications

Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

PPARγ polymorphisms and cancer risk: A meta-analysis involving 32,138 subjects

Prevalence of the rs1801282 single nucleotide polymorphism of the PPARG gene in patients with metabolic syndrome

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