Pro12Ala Polymorphism Of PPARγ2 Gene Research Articles

Association of Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) Gene with Type 2 Diabetes Mellitus in Ethnic Kashmiri Population.

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia associated with insulin resistance and relative insulin deficiency. T2DM is believed to be attributable to the combined effect of genetic and environmental factors. Peroxisome proliferator-activated receptor gamma 2 (PPARγ2) is one of the main candidate genes that are implicated in T2DM. A common proline 12 alanine (Pro12Ala) polymorphism in PPARγ2 has been shown to be associated with T2DM. The aim of this work was to investigate the possible role of PPARγ2 gene polymorphism, as a genetic risk factor for T2DM. The study comprised 200 ethnic unrelated subjects (100 T2DM patients and 100 controls). PCR-RFLP technique was used for genotyping analysis. The frequency of the Pro allele was 79 and 91.5% for controls and cases, respectively (P<0.05; OR 3.2; 95% CI 1.64-6.3). The Pro12Ala polymorphism was in Hardy-Weinberg equilibrium in both patients and controls (χ 2=0.13,P>0.05). We found a significant association of Pro12Ala polymorphism of PPARγ2 gene with T2DM, however the genotypes showed statistically significant association only with few clinical parameters including body mass index, total cholesterol, and low-density lipoprotein (P<0.05). The study signifies that Pro allele in PPARγ2 may be a genotypic risk factor that confers susceptibility to T2DM in ethnic Kashmiri population.

PP.28.18

Objective:To determine association of insertional-deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene (dbSNP id: rs4646994) and Pro12Ala polymorphism of PPAR-γ2 gene (dbSNP id: rs1801282) with functional activity of pancreatic β-cells and insulin resistance (IR) in patients with

Effects of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ2 gene on metabolic syndrome risk: A meta-analysis

BackgroundAssociations between peroxisome proliferator-activated receptor γ2 (PPARγ2) gene polymorphism and metabolic syndrome risk remained controversial and ambiguous. Thus, we performed a meta-analysis to assess the association between Pro12Ala polymorphism in PPARγ2 gene and metabolic syndrome susceptibility. MethodsAn electronic literature search was conducted on Medline, OVID, Cochrane Library database, and the China National Knowledge Internet up to March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the fixed or random effects model. ResultsTen studies involving a total of 4456 cases and 10343 controls were included in this meta-analysis. No statistical evidence of association was found between Pro12Ala polymorphism and metabolic syndrome risk in all genetic models (homozygote model: OR=0.83, 95% CI=0.62–1.12; heterozygote model: OR=1.04, 95% CI=0.94–1.14; dominant model: OR=1.02, 95% CI=0.93–1.12; recessive model: OR=0.83, 95% CI=0.62–1.11). No statistical evidence of significant association was observed when stratified by ethnicity, definition of metabolic syndrome, source of control groups and quality score of the selected articles. All in all, the results did not support a major role of the Pro12Ala variant of the PPARγ2 gene in metabolic syndrome risk. ConclusionsThis meta-analysis suggested that the effect of Pro12Ala polymorphism in PPARγ2 gene may not be related to metabolic syndrome as an entity. However, Pro12Ala may affect the single component of metabolic syndrome. A large, well designed study is required to more adequately assess the role for Pro12Ala polymorphism on metabolic syndrome.

The association between the PPARγ2 Pro12Ala polymorphism and nephropathy susceptibility in type 2 diabetes: a meta-analysis based on 9,176 subjects

BackgroundThe polymorphism Pro12Ala in peroxisome proliferator-activated receptor­γ2 gene (PPARγ2) has been reported to be associated with diabetic nephropathy (DN) in some studies, though the results remain inconclusive. To explore this relationship between PPARγ2 Pro12Ala polymorphism and the susceptibility for DN, a cumulative meta-analysis was performed in this study.MethodPubMed, Medline, Embase and Web of Science databases have been systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Results18 studies were included in this meta-analysis, involving 3,361 cases and 5,815 controls. The PPARγ2 Ala12 allele was significantly associated with decreased risk of DN based on dominant model (OR=0.778; 95%CI=0.618–0.981; Pheterogeneity=0.008; P=0.034). In the stratified analysis by ethnicity, significantly decreased risks were found among Caucasians for dominant model (OR=0.674; 95%CI=0.500–0.909; Pheterogeneity=0.079; P=0.010), while there was no significant association was found in Asians.ConclusionsThe results from the present meta-analysis indicated that the Pro12Ala polymorphism in PPARγ2 gene is not a risk factor for DN in type 2 diabetes (T2D). Further large and well-designed studies are needed to confirm this conclusion.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7491348341027320.

Association between PRO12ALA polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in Iranian patients

BACKGROUND:Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. It has been shown that an association exists between Proline 12 alanine (Pro12Ala) polymorphism of PPAR-GAMMA2 (PPAR-γ2) gene and increased risk of type 2 diabetes mellitus (T2DM) in different populations. Therefore, the present study was designed to investigate the association between Pro12Ala polymorphism of PPAR-γ2 gene and T2DM in an Iranian population.MATERIALS AND METHODS:Two hundred unrelated people, including 100 healthy controls and 100 diabetic patients were recruited diagnosed based on American Diabetes Association criteria. Blood samples were used for isolation of genomic deoxyribonucleic acid (DNA). Having extracted the genomic DNA from human blood leukocytes by means of High Pure polymerase chain reaction (PCR) Template preparation kit, we carried out polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on each blood sample. Then, Genomic DNA was digested by BstU-I restriction enzyme. Thereafter, restriction products were analyzed by means of Polyacrylamide gel electrophoresis and stained by Ethidium Bromide.RESULTS:We found that the frequency of Ala allele in healthy subjects was significantly higher than in diabetic subjects (P = 0003). Moreover, the genotype frequency of Ala/Ala in healthy subjects was significantly higher than in diabetic subjects (P < 0.001). However, the genotype frequency of Ala/Pro in diabetic subjects was significantly higher than in healthy subjects (P < 0.001).CONCLUSION:The present study suggests that polymorphism of PPAR-γ2 gene is associated with T2DM. Furthermore, Ala allele is significantly found in non-diabetic individual’s Iranian population.

Association of Peroxisome Proliferator‐Activated Receptor‐Gamma 2 Pro12Ala Polymorphism with Advanced‐Stage Endometriosis

To investigate whether the peroxisome proliferator-activated receptor (PPAR)-γ2 Pro12Ala polymorphism is associated with a risk of advanced-stage endometriosis in a Korean population. Case-control study in a collective of 446 patients and 427 controls. The Pro12Ala polymorphism of PPAR-γ2 gene was genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The distribution of the PPAR-γ2 Pro12Ala polymorphism was different between the advanced-stage endometriosis group and the control group (non-CC rates were 5.2% for patients with advanced endometriosis and 10.1% for the control group, respectively, P = 0.006). The frequency for the Ala-12 allele variant was significantly lower in patients with advanced stage of endometriosis (2.7%) than in the control group (5.3%) (P = 0.006). These findings suggest that the PPAR-γ2 Pro12Ala polymorphism is associated with advanced-stage endometriosis in the Korean population. Unlike results from other studies reported so far, the Ala-12 allele may have protective effects against advanced-stage endometriosis in the Korean population.

The Pro12Ala Polymorphism in PPARγ2 Gene Affects Lipid Parameters in Greek Primary School Children: A Case of Gene-to-Gender Interaction

In the present study we sought to evaluate the impact of the PPAR-gamma2 Pro12Ala polymorphism on blood lipid levels of primary school children. 81 male and 92 female schoolchildren were genotyped. Biochemical, anthropometric, and lifestyle variables were assessed. 14.1% females and 14.8% males were heterozygotes, while the rest of the subjects were homozygotes for the Pro allele. A significant interaction between the PPARgamma-2 gene and gender on blood lipid levels was detected. In particular, Pro/Pro females exhibited higher values of total cholesterol (194 +/- 32 vs 180 +/- 28 mg/dL, P = 0.06) and triglycerides (94 +/- 31 vs 77 +/- 11 mg/dL, P = 0.045) compared to Pro/Ala individuals. The gene-to-gender interaction term was highly significant (P < 0.001). On the other hand, Pro/Pro males showed higher values of HDL cholesterol (47 +/- 8 vs 43 +/- 9 mg/dL, P = 0.001), lower total cholesterol/HDL ratio (4.04 +/- 0.59 vs 4.45 +/- 0.61, P = 0.031), lower values of apoB (59.8 +/- 11.3 vs 66.8 +/- 6.6 mg/dL, P = 0.007) and lower values of apoB/apoA1 ratio (0.41 +/- 0.09 vs 0.48 +/- 0.08, P = 0.019) compared with Pro/Ala. Even after adjusting for body mass index (BMI), total energy intake, total fat intake and saturated fat intake, differences in total cholesterol/high-density lipoprotein (HDL) cholesterol and the apoB/apoA1 ratios remained significant. Regarding females, no differences were observed among genotypes concerning total cholesterol/HDL levels (P for gene-to-gender interaction = 0.001) and the apoB/apoA1 levels (P for gene-to-gender interaction = 0.029). We show for the first time a gene-to-gender interaction on total cholesterol/HDL and apoB/apoA1 ratios, in male schoolchildren genotyped for PPAR-gamma2 Pro12Ala.

Lack of Association between the Pro12Ala Polymorphism in PPAR-γ2 Gene and Body Weight Changes, Insulin Resistance and Chronic Diabetic Complications in Obese Patients with Type 2 Diabetes

It is generally accepted that the Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with an increased risk of type 2 diabetes. However, studies on an association between the polymorphism and obesity have yielded inconsistent findings. Also, a role of PPAR-gamma receptors in development of chronic diabetic complications cannot be excluded. The aim of this study was to investigate an association between Pro12Ala polymorphism and body weight changes, insulin resistance, insulin secretion and incidence of diabetic complications in obese patients with long-lasting type 2 diabetes. In 216 obese patients with at least a 10-year history of type 2 diabetes, a detailed medical history was taken and a physical examination with assessment of diabetic complications was performed as well as evaluation of insulin resistance (homeostatic model assessment-HOMA), insulin secretion and other biochemical parameters. PCR-RFLP was used to assess Pro12Ala polymorphism. Two subgroups of patients were compared: homozygotic Pro/Pro and Ala allele carriers (Ala/Ala + Ala/Pro). No differences between the analyzed groups in body weight changes, insulin resistance and insulin secretion were found, but Ala allele was significantly more frequent in males than in females. There was no difference in incidence and progression of diabetic complications with only a trend towards higher incidence of diabetic retinopathy in patients with Ala allele. There is no association between Pro12Ala PPAR-gamma2 polymorphism and body mass changes observed during a course of type 2 diabetes, differences in peripheral insulin resistance and incidence and progression of diabetic complications in obese patients with long-lasting type 2 diabetes.

Polymorphisms of the peroxisome proliferator–activated receptor-γ and its coactivator-1α genes in Chinese women with polycystic ovary syndrome

The polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and its coactivator-1 (Gly482Ser) genes were investigated among 201 Chinese Han women with polycystic ovary syndrome (PCOS) and among 147 regularly cycling women as control subjects. We did not find statistically significant differences with peroxisome proliferator-activated receptor-gamma2 Pro12Ala and peroxisome proliferator-activated receptor-gamma-1alpha Gly482Ser polymorphism distributions between Chinese women with PCOS and controls, or with body mass index and reproductive hormones among various genotypic groups of PCOS, suggesting that these genetic mutants did not have an effect on the susceptibility to PCOS.

W02-P-003 The PRO12ALA polymorphism in PPARγ2gene affects lipid ratios in Greek children; a case of gene-gender interaction

W02-P-003 The PRO12ALA polymorphism in PPARγ2gene affects lipid ratios in Greek children; a case of gene-gender interaction

The Pro12Ala polymorphism of PPARγ2 gene and susceptibility to type 2 diabetes mellitus in a Polish population

Introduction: It has recently been shown that polymorphisms of some genes might influence the genetic susceptibility to complex, multifactorial forms of type 2 diabetes mellitus (T2DM). One of those genes is peroxisome proliferator activated receptor γ (PPARγ). The PPARγ gene product is a nuclear hormone receptor that regulates adipogenesis and is a target for thiazolidinediones, medications enhancing sensitivity to insulin. The Pro12Ala amino acid variant of the PPARγ2 isoform is associated with T2DM in several populations. Aims: (1) To determine the allele and genotype frequency of the Pro12Ala PPARγ2 amino acid variant in a Polish population; (2) To search for the association of the Pro12Ala polymorphism with T2DM in the examined population. Methods: We included 644 individuals in this study: 366 T2DM patients with age of diagnosis greater than 35 years and 278 non-diabetic control subjects. The fragment of the PPARγ2 gene which contains the examined amino acid variant was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by the specific restriction enzyme BshI. Differences in distribution between the groups were examined by χ 2 test. Results: The frequency of Pro/Ala alleles was similar in T2DM patients and in the control subjects (83.5%/16.5% vs. 84.5%/15.5%, respectively, P=0.607). Similarly, there was no difference between the groups when we analysed the genotype distribution. Stratification analyses based on age of diagnosis, body mass index (BMI), and family history of T2DM were performed. The Pro/Ala and Ala/Ala genotypes tended to be more frequent in T2DM cases with age of diagnosis >50 years than in controls (36.2% vs. 27.3%, P=0.046). This difference was not significant after Sheffe correction for multiple comparisons. The other stratification analyses did not show any difference between the groups. Conclusion: The frequency of the Pro12Ala PPARγ2 polymorphism in the Polish population studied is similar to that in other Caucasian populations. In the case-control study, we were not able to confirm earlier reports that the Pro allele conferred an increased risk for development of T2DM. Moreover, the results of the stratified analysis suggest an opposite trend in late onset T2DM.