Pro12Ala Polymorphism of the Peroxisome ProliferatorActivated Receptor-.GAMMA. Gene is Associated With Metabolic Syndrome and Surrogate Measures of Insulin Resistance in Healthy Men  Interaction With Smoking Status

Tellechea, Mariana Lorena; Aranguren, Florencia; Pérez, Mario Noa; Cerrone, Gloria Edith; Frechtel, Gustavo Daniel; Taverna, Mariano J.

doi:10.1253/circj.cj-09-0320

Cited by 32 publications

(30 citation statements)

References 55 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some de scribe that the presence of polymorphisms confers a protective effect with respective do type 2 diabetes risk (12), whereas others indicate that it is associated with increased susceptibility to the disease (8,13). There are also studies in which no association was found be tween this variant and the frequency of type 2 diabetes (14 16).…”

Section: Introductionmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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

show abstract

Section: Introductionmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

show abstract

“…Namely, the type 2 diabetes risk allele of PPARG rs1801282 previously found to associate with insulin resistance [11,12] and the ADCY5 variant previously found to associate with birthweight and fasting glucose apart from HOMA-B [13,14]. The major allele of G6PC2 rs560887 was associated with decreased HOMA-B as well as increased insulinogenic index.…”

Section: Discussionmentioning

confidence: 94%

Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data

et al. 2015

View full text Add to dashboard Cite

Aims/hypothesis We examined the extent to which surrogate measures of insulin release have shared genetic causes. Methods Genetic and phenotypic correlations were calculated in a family cohort (n=315) in which beta cell indices were estimated based on fasting and oral glucose-stimulated plasma glucose, serum C-peptide and serum insulin levels. Furthermore, we genotyped a large population-based cohort (n= 6,269) for common genetic variants known to associate with type 2 diabetes, fasting plasma glucose levels or fasting serum insulin levels to examine their association with various indices. Results We found a notable difference between the phenotypic and genetic correlations for the traits, emphasising that the phenotypic correlation is an insufficient measure of the magnitude of shared genetic impact. In addition, we found that corrected insulin response, insulinogenic index and incAUC for insulin after an oral glucose challenge shared the majority of their genetic backgrounds, with genetic correlations of 0.80-0.99. The BIGTT index for acute insulin response differed slightly more from the latter with genetic correlations of 0.78-0.87. The HOMA for beta cell function was genetically closely related to fasting insulin with a genetic correlation of 0.85. The effects of 82 selected susceptibility single nucleotide polymorphisms on these insulin secretion indices supported our interpretation of the data and added insight into the biological differences between the examined traits. Conclusions/interpretation The level of shared genetic background varies between surrogate measures of insulin release, and this should be considered when designing a genetic association study to best obtain information on various mechanisms of insulin release.

show abstract

“…These results suggested that polymorphisms at the rs3856806 locus were associated with the occurrence of MS in Kazakhs, and the C allele was a risk factor for MS. In contrast, Tellechea et al (2009) studied 572 Argentinean people and found that polymorphisms at the rs1801282 locus were associated with the incidence of MS. They also found that smoking increased the likelihood of developing MS. Huguenin and Rosa (2010) conducted a meta-analysis and found that rs1801282 polymorphisms were associated with diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic susceptibility is also a major cause of MS. Recent reports have shown a correlation between polymorphisms in peroxisome proliferator activated receptor γ (PPARγ) and components of MS, such as hypertension, diabetes and obesity; however, the conclusions from these studies are inconsistent (Tellechea et al, 2009;Huguenin and Rosa, 2010;Bego et al, 2011). Whether polymorphisms at multiple loci of the PPARγ gene are related to the occurrence of MS in Uyghurs and Kazakhs remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the PPARγ gene and their association with metabolic syndrome in Uyghurs and Kazakhs from Xinjiang, China

Chen

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. We investigated the association between polymorphisms rs1801282 and rs3856806 of the PPARγ gene and metabolic syndrome (MS) among Uyghurs and Kazakhs. Mass spectrometry techniques were used to detect the PPARγ genotypes rs1801282 and rs3856806 in 987 subjects, CC genotype and C allele frequencies were 83.6 and 91.7%, respectively, at rs1801282 in Kazakhs, which were higher than those in Uyghurs (72.3 and 85.0%, respectively; P < 0.05). CC genotype and C allele frequencies were 73.6 and 85.3%, respectively, at the rs3856806 loci in Kazakhs, which were higher than those in Uyghurs (60.7 and 77.9%, respectively; P < 0.05). For the rs3856806 polymorphism in Kazakhs, CT/TT genotype and T allele frequencies were 21.2 and 12.4% for MS subjects, which were lower than those for the control group (31.6 and 17.0%, respectively; P < 0.05). Risk analysis of Kazakhs revealed that individuals with the CT and TT genotypes at rs3856806 had an increased risk, 0.524-and 0.770-fold, respectively, of developing MS than those possessing the CC genotype. Individuals with the T allele also had an increase in risk, by 0.699-fold, of developing MS than those with the C allele. For Uyghurs, those with the CC genotype at rs1801282 had higher systolic blood pressure than those with the CG/GG genotype. Among Kazakhs, those with the CC genotype at rs3856806 had higher triglyceride and waist-hip ratio levels but lower high-density lipoprotein cholesterol levels than those with the CT/TT genotype. The rs1801282 and rs3856806 PPARγ polymorphisms differ between Uyghurs and Kazakhs from Xinjiang Province, China.

show abstract

Pro12Ala Polymorphism of the Peroxisome ProliferatorActivated Receptor-.GAMMA. Gene is Associated With Metabolic Syndrome and Surrogate Measures of Insulin Resistance in Healthy Men Interaction With Smoking Status

Cited by 32 publications

References 55 publications

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

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

Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data

Polymorphisms in the PPARγ gene and their association with metabolic syndrome in Uyghurs and Kazakhs from Xinjiang, China

Contact Info

Product

Resources

About