Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes.

Mancini, Francesco Paolo; Vaccaro, Olga; Sabatino, Lina; Tufano, Antonella; Rivellese, Angela Albarosa; Riccardi, Gabriele; Colantuoni, Vittorio

doi:10.2337/diabetes.48.7.1466

Cited by 150 publications

(113 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a previous study we could not ®nd an association of the Pro12Ala mutation with overweight in a population-based sample. 11 In agreement with the hypothesis that the Pro12Ala mutation plays a much stronger role in severe obesity with early onset, a very recent paper by Ek et al shows a signi®cant and positive association between the occurrence of the Pro12Ala mutation and BMI in people with severe obesity with juvenile onset, although in the condition of homozygosity. 19 As for insulin resistance we could not ®nd any association between insulin concentration, which is a marker of insulin resistance, and the Ala-mutated allele.…”

Section: Discussionsupporting

confidence: 56%

Pro12Ala mutation in the peroxisome proliferator-activated receptor γ2 (PPARγ2) and severe obesity: a case–control study

et al. 2000

Self Cite

View full text Add to dashboard Cite

OBJECTIVE: To explore the association of the Pro12Ala mutation in the peroxisome proliferator-activated receptor g g g2 with severe obesity and the features of the metabolic syndrome in a population-based sample of Caucasians. PARTICIPANTS AND METHODS: The study is based on a case ± control design: 95 non-diabetic severely obese (body mass index, BMI b 35 kgam 2 ) cases and 280 normal weight (BMI`25 kgam 2 ), age-and sex-matched controls selected from the same population were studied. Height, weight, waist circumference, as well as blood pressure were measured according to a standard protocol. BMI at age 25 y was calculated on the basis of current height and reported weight at age 25 y Biochemical measurements included fasting glucose, triglycerides, high-density lipoprotein cholesterol and insulin. DNA analysis was conducted by PCR and gel electrophoresis. RESULTS: Age and gender distribution were similar in obese and normal weight participants. The percentage of people with the Pro12Ala mutation was not signi®cantly different in obese or normal weight participants (20% and 15%, respectively; P 0.32). Conversely, in obese participants with obesity starting in early adulthood (ie with BMI at age 25 above 26.9 kgam 2 which represents the median of the whole obese group), the Pro12Ala mutation was observed signi®cantly more frequently than in the normal weight controls (29% vs 15%; chi square 4.5, P`0.05; odds ratio 2.4; 95% CI 1.03 ± 5.36). No association of the Pro12Ala variant with any of the component of the metabolic syndrome measured in the study was observed in either obese, juvenile obese or normal weight participants. CONCLUSIONS: Results of this study indicate that the Pro12Ala mutation does not play a major role as a determinant of severe obesity andaor features of the metabolic syndrome in the general population. However, this mutation may be of greater importance as a contributor to early onset obesity.

show abstract

Section: Discussionsupporting

confidence: 56%

Pro12Ala mutation in the peroxisome proliferator-activated receptor γ2 (PPARγ2) and severe obesity: a case–control study

et al. 2000

Self Cite

View full text Add to dashboard Cite

show abstract

“…In vitro studies showed that this allele reduces PPARg DNA binding affinity and transcriptional activity [70,73,194,195]. Although some additional studies did not support a statistically significant role for the PPARg 2 P12A polymorphism in the etiology of type 2 diabetes [196][197][198], a more recent meta-analysis of all published data, comprising more than 25 000 cases of diabetes, showed an association of P12A with type 2 diabetes [199]. The large population that was necessary in order to demonstrate the association between P12A and type 2 diabetes is due to the weak effect of the risk allele, since individuals that are homozygous for the higher risk P12 allele have only a 25% increase in diabetes risk.…”

Section: Pparg Loss Of Function Mutationsmentioning

confidence: 99%

Fat poetry: a kingdom for PPARγ

2007

View full text Add to dashboard Cite

Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor g (PPARg), which is a fatty acid-and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARg agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARg in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARg modulators.

show abstract

“…The most frequently occurring PPAR-γ polymorphism is the substitution of proline to alanine (Pro12Ala) in exon B of the PPAR-γ2 gene (rs1801282), and numerous polymorphism studies have been performed on its association with type 2 diabetes mellitus, insulin resistance and obesity, although the significance of such associations remains still a debate (Fajas et al, 1997;Mancini et al, 1999;Ringel et al, 1999;Altshuler et al, 2000;Clement et al, 2000;Hara et al, 2000;Meirhaeghe et al, 2000). The next most frequently occurring PPAR-γ polymorphism is C → T substitution in exon 6 (rs3856806), which was identified by Meirhaegue et al (2000), and it was shown to have significant association with bone mineral density (BMD) in postmenopausal Japanese women (Ogawa et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The association of Pro12Ala polymorphism of peroxisome proliferator-activated receptor-γ gene with serum osteoprotegerin levels in healthy Korean women

Rhee

Oh²,

Yun³

et al. 2007

Exp Mol Med

View full text Add to dashboard Cite

Recent evidences suggest that the activation of peroxisome proliferator-activated receptor (PPAR)-γ, which is an important transcriptional factor in adipocyte differentiation, also plays an important role in the bone microenvironment. The objective of the study was to clarify whether Pro12Ala polymorphism was related to the serum OPG levels and bone mineral metabolism in healthy Korean women. In 239 Korean women (mean age 51 years), who participated in medical check-up program in a health promotion center, anthropometric measurements, lumbar spine and femoral neck bone mineral density (BMD), bone turnover markers, such as serum total alkaline phosphatase (ALP) levels, urine deoxypyridinoline levels, and 24-h urine calcium excretion were measured. Serum levels of OPG were measured with ELISA method. DNAs were extracted from the samples and the genotyping of the Pro12Ala polymorphism (rs1801282) in the PPAR-γ gene was performed via an allelic discrimination assay using a TaqMan probe. In addition, we examined the haplotype analysis between two polymorphisms of PPAR-γ gene, Pro12Ala in exon B and C161T in exon 6 (rs3856806). Allelic frequencies were 0.950 for Pro allele and 0.050 for Ala allele, which was in compliance with HardyWeinberg equilibrium, and there was no Ala12Ala genotype among the genotyped subjects. Mean serum OPG level was significantly lower (P = 0.035), and serum total ALP was significantly higher (P = 0.014) in the Pro12Ala genotype group compared with the Pro12Pro genotype group, which were consistently significant even after adjustment for weight, height, and serum follicle stimulating hormone (FSH). In multiple regression analysis with serum OPG as the dependent variable and age, weight, ALP, femoral neck BMD and Pro12Ala genotype included in the model, only Pro12Ala genotype was significant determinant of serum OPG level (β = 0.136, P = 0.035). The haplotype analysis with C161T polymorphism revealed that subjects with Ala and T alleles showed significantly lower serum OPG levels compared with those with Pro12Pro/CC genotype, which were consistently significant even after adjustment for age, weight, height and FSH (P = 0.010). This result suggests statistically significant association of Pro12Ala polymorphisms with serum OPG levels in Korean females.

show abstract

Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes.

Cited by 150 publications

References 8 publications

Pro12Ala mutation in the peroxisome proliferator-activated receptor γ2 (PPARγ2) and severe obesity: a case–control study

Pro12Ala mutation in the peroxisome proliferator-activated receptor γ2 (PPARγ2) and severe obesity: a case–control study

Fat poetry: a kingdom for PPARγ

The association of Pro12Ala polymorphism of peroxisome proliferator-activated receptor-γ gene with serum osteoprotegerin levels in healthy Korean women

Contact Info

Product

Resources

About