PPARγ Pro12Ala Polymorphism Research Articles

Peroxisome proliferators-activated receptor gamma polymorphisms and colorectal cancer risk.

Several studies evaluated the association between peroxisome proliferators-activated receptor gamma (PPARγ) Pro12Ala (rs1801282), and His477His (rs3856806) polymorphisms and the risk of colorectal cancer (CRC). However, the results were not stable. We searched databases containing PubMed and EMBASE. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A significantly decreased CRC risk was found for PPARγ Pro12Ala polymorphism (OR = 0.88, 95% CI 0.83-0.94, P < 0.0001). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.89, 95% CI 0.83-0.95, P = 0.0003) but not in Asian population (OR = 0.76, 95% CI 0.57-1.02, P = 0.07). In the subgroup analysis by CRC location, significantly decreased risks were found in rectal cancer (OR = 0.88, 95% CI 0.77-1.00, P = 0.05) and colon cancer (OR = 0.82, 95% CI 0.73-0.92, P = 0.0008). In addition, a significantly decreased CRC risk was also detected for PPARγ His477His polymorphism (OR = 0.66, 95% CI 0.44-1.00, P = 0.05). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.43, 95% CI 0.26-0.69, P = 0.0006) but not in Asian population (OR = 0.95, 95% CI 0.73-1.25, P = 0.72). PPARγ Pro12Ala and His477His polymorphisms might be associated with susceptibility of CRC.

Impact of PPARG (Pro12Ala) Polymorphism on Early Debut of Obesity in Children

Impact of PPARG (Pro12Ala) Polymorphism on Early Debut of Obesity in Children

ASSOCIATION OF THE HUMAN PPARγ2 PRO12ALA POLYMORPHISM WITH OBESITY IN A POPULATION FROM TURKEY.

There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the gender-stratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.

The Association of PPARγ Pro12Ala and C161T Polymorphisms with Polycystic Ovary Syndrome and Their Influence on Lipid and Lipoprotein Profiles.

BackgroundThe aim of present study was to clarify the role of the peroxisome proliferator-activated receptor (PPAR) γ Pro12Ala and C161T polymorphisms in the pathogenesis of polycystic ovary syndrome (PCOS) and their influence on lipid and lipoprotein profiles of patients.Materials and MethodsThe present cross-sectional study consisted of 50 women with PCOS, who referred to the Kermanshah University of Medical Sciences Clinic between April and October 2015, and 233 unrelated age-matched healthy women from the same region (West Iran). The PPARγ Pro12Ala and PPARγ C161T polymorphisms were gen- otyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood sugar (FBS), serum triglycerides (TG), cholesterol, low density lipoprotein- cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C) and estradiol levels were measured.ResultsThe serum level of estradiol was significantly lower in PCOS patients compared to healthy women. The PPARγ Pro12Ala (CG) genotype increased the risk of PCOS 2.96-fold. The frequency of the PPARγ T allele (at C161T) was 21% in patients and 17.2% in controls with no significant difference (P=0.52). In all studied individuals, the PPARγ CG geno- type was associated with significantly higher levels of TG. However, significantly lower levels of total cholesterol and LDL-C were observed in PPARγ TT individuals compared with those with the CC genotype. Within the PCOS group, the PPARγ CG genotype was significantly associated with lower levels of estradiol compared with the CC genotype. Also, the CG genotype was significantly associated with higher levels of TG when compared with the CC genotype.ConclusionOur study shows that, unlike PPARγ C161T, PPARγ Pro12Ala is associated with the risk of PCOS. Also, we found that the lipid and lipoprotein profiles significantly vary based on PPARγ Pro12Ala and C161T genotypes.

PPARγ Pro12Ala and C161T polymorphisms in patients with acne vulgaris: Contribution to lipid and lipoprotein profile

PurposeThe aim of present study was to clarify the role of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala and C161T variants in the pathogenesis of acne vulgaris (AV) and their influence on lipid and lipoprotein profile. MethodsThe present case-control study consisted of 393 individuals including 198 patients with AV (mild-, moderate-, and severe-AV) and 195 unrelated age-matched healthy individuals from Western Iran. The PPARγ Pro12Ala and C161T polymorphisms were identified using polymerase chain reaction-restriction length polymorphism method. Also, serum lipid and lipoprotein profile and fasting blood sugar (FBS) were detected in studied individuals. ResultsIn women patients with AV significantly higher serum levels of FBS, total cholesterol, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol compared to healthy women were detected. Neither PPARγ Pro12Ala nor C161T polymorphism was associated with the risk of AV but the Pro allele was a risk factor for AV among all men and women patients ≥20years. The variant genotype of PPARγ CG (Pro/Ala) was associated with significantly higher levels of total cholesterol and triglycerides compared to CC (Pro/Pro) genotype. We detected a significantly lower level of FBS in the presence of CT+TT genotype of PPARγ C161T compared to CC genotype. Also, carriers of PPARγ TT genotype had significantly lower serum level of total cholesterol and LDL-C compared to CC genotype. ConclusionsOur results demonstrated the association of PPARγ Pro allele with susceptibility to AV in patients ≥20years and the influence of PPARγ Pro12Ala and C161T polymorphisms on the lipid and lipoprotein profile.

Quantitative evaluation of PPAR-γ2 Pro12Ala polymorphism with hypertension.

The peroxisome proliferator-activated receptor γ2 (PPARγ2)Pro12Ala polymorphism has been reported to be associated with hypertension. However, relevant studies have shown inconsistent results. To quantitatively evaluate the relationship between the PPARγ2Pro12Ala polymorphism and hypertension risk, we conducted ameta-analysis based on all available studies selected from Scopus, Web of Science, PubMed, Chinese National Knowledge Infrastructure, and Wanfang databases. In all, 13 studies were finally included in this meta-analysis. In the allelic model (Ala vs. Pro), the Ala allele of PPARγ2 Pro12Ala polymorphism was associated with hypertension (Odds Ratio [OR]= 0.723, 95% confidence interval [CI]= 0.607-0.861). Sensitivity analysis and exclusion of studies with poor quality scores or controls complicated by other diseases confirmed the validity of this association. Moreover, the PPARγ2Pro12Ala polymorphism was associated with hypertension in the codominant (OR= 0.710, 95% CI= 0.626-0.806), recessive (OR= 0.561, 95% CI= 0.418-0.754), and dominant (OR= 0.693, 95% CI= 0.577-0.833) models. The Ala allele appears to have aprotective effect against hypertension and adominant function.

Peroxisome proliferator-activated receptor-γ polymorphism (rs1801282) is associated with obesity in Egyptian patients with coronary artery disease and type 2 diabetes mellitus.

ObjectivePeroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene is one of the possible genes linking diabetes mellitus (DM) with coronary artery disease (CAD). The aim of this study is to clarify whether PPAR-γ Pro12Ala polymorphism is associated with the development of CAD in type 2 diabetic patients and to evaluate PPAR-γ Pro12Ala polymorphism genetic distribution in type 2 DM (T2DM) Egyptian subjects.MethodsPPAR-γ Pro12Ala polymorphism was determined by Real-Time PCR in serum of 405 subjects classified into 4 groups; T2DM patients (n = 105), T2DM with CAD (n = 100), CAD patients (n = 100) and healthy controls (n = 100).ResultsThe PPAR-γ Pro12Ala polymorphism was associated significantly with T2DM with CAD (group2) (OR = 3, 95% CI = (1.5–6); p = 0.001). In this study, T2DM with CAD complications carrying the PPAR-γ Pro12Ala polymorphism had higher BMI than those without the PPAR-γ Pro12Ala polymorphism (p < 0.0001). CAD patients carrying PPAR-γ Pro12Ala polymorphism had considerable insulin resistance features. Plasma paraoxanase 1(PON1) level was considerably reduced among our 3 studied groups in comparison to control group (p < 0.001).ConclusionsPPAR-γ Pro12Ala polymorphism might represent a novel risk factor for CAD in T2DM.

Associations between PPARG polymorphisms and the risk of essential hypertension.

BackgroundPeroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the pathogenesis and maintenance of essential hypertension (EH). It has been suggested that polymorphisms of PPARG are associated with the risk of EH. However, findings to date remain controversial. To elucidate the associations between the PPARG Pro12Ala and C161T polymorphisms and EH risk, a meta-analysis was carried out.MethodsA comprehensive literature search of PubMed, Embase, CNKI (Chinese National Knowledge Infrastructure), VIP and Wanfang databases was conducted. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated to estimate the size of the effect using the random-effects model. At the same time, the pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of the PPARG Pro12Ala polymorphism and blood pressure.ResultsFinally, Fifteen papers (seventeen studies) including 4,151 cases and 4,997 controls to evaluate the association of the PPARGPro12Ala polymorphism and EH risk, were included in this study. Overall, the results suggested that Ala allele was associated with the decreased EH risk (for allelic model, OR = 0.757, 95%CI: 0.624–0.918, P = 0.005; for dominant model, OR = 0.771, 95%CI: 0.627–0.946, P = 0.013). The subgroup analysis stratified by ethnicity showed that the significant association between the PPARG Pro12Ala polymorphism and EH was only detected in the Asian subgroup. There was no difference in blood pressure values between Ala carriers and non-carriers. For the C161T polymorphism, only 5 studies comprising 1,118 cases and 1,357 controls met the inclusion criteria. The overall results showed that the PPARG C161T polymorphism was not associated with the risk of EH. But in the subgroup analysis, we found that the PPARG C161T polymorphism significantly associated with the risk of EH in the Asian subgroup (for allelic model, OR = 0.719, 95% CI: 0.537–0.963, P = 0.027; for dominant model, OR = 0.653, 95% CI: 0.439–0.972, P = 0.036).ConclusionOur meta-analysis suggested that the PPARG polymorphisms might be associated with the risk of EH.

Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Pro12Ala Gene Polymorphism and Oxidative Stress in Menopausal Women with Cardiovascular Disease from North Indian Population of Punjab

The present paper investigated the association of PPARγ Pro12Ala polymorphism with cardiovascular disease (CVD) and oxidative stress (OS) in menopausal women from North Indian population of Punjab....

DHA-enriched fish oil upregulates cyclin-dependent kinase inhibitor 2A (P16INK) expression and downregulates telomerase activity without modulating effects of PPARγ Pro12Ala polymorphism in type 2 diabetic patients: A randomized, double-blind, placebo-controlled clinical trial

The present study investigated the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on telomerase activity, mRNA expression of P16INK, IL-6, and TNF-α considering Pro12Ala polymorphism in the PPARγ gene. In this double-blind randomized controlled trial, 72 PPARγ Pro12Ala polymorphism genotyped type 2 diabetic patients aged 30-70 years were randomly assigned to receive 2.4 gr of DHA-enriched fish oil or a placebo for 8 weeks. Genotyping of the Pro12Ala polymorphism in the PPARγ gene was assessed using polymerase chain reaction-restriction length polymorphism (PCR-RFLP), telomerase activity in the peripheral blood mononuclear cell (PBMC) was measured using PCR-ELISA based on the telomeric repeat amplification protocol (TRAP), and changes in the mRNA expression of P16, IL-6, and TNF-α were measured using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). In the DHA group, telomerase activity was decreased (p=0.001) during the intervention. In addition, between-group comparisons showed significant differences in the changes in telomerase activity (p=0.003) and P16 mRNA expression (p=0.028) and non-significant differences in TNF-α and IL-6 mRNA expression. The gene*DHA interaction could not affect changes in P16, IL-6, or TNF-α mRNA expression or in telomerase activity in PBMC. Short-time DHA-enriched fish oil supplementation caused increased levels of P16 expression and a decline in telomerase activity compared with the control group without modulating the effects of Pro12Ala polymorphism on the PPARγ gene. Because of the positive correlation between P16 activity and cellular senescence, the possibility of senescence stimulation by DHA is proposed.

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.

The Pro12Ala polymorphism in the PPAR-γ2 gene is not associated to obesity and type 2 diabetes mellitus in a Cameroonian population.

BackgroundPeroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) is a transcription factor with a key role in adipocyte differentiation, lipid storage and glucose homeostasis. The Ala allele of the common Pro12Ala polymorphism in the isoform PPAR-γ2 is at the center of many controversies because in some populations, it has been observed to be associated with T2DM or obesity but, not in others. The aim of this study was to investigate the association of Pro12Ala polymorphism in the PPAR-γ2 gene with susceptibility to obesity or T2DM in a Cameroonian population.MethodsThis case-control study included 62 obese, 60 T2DM patients and 120 controls (60 non obese and 60 patients without T2DM), all unrelated and of Cameroonian origin. PPAR-γ2 was examined by genotyping for Pro12Ala using the Restriction Fragment Length Polymorphism - Polymerase Chain Reaction (PCR - RFLP).ResultsA portion of the 270 base pair bands of the PPAR-γ2 gene was successfully amplified. The Ala12 variant was totally absent from the study population, all participants being homozygote Pro/Pro.ConclusionPPAR-γ2 Pro12Ala gene polymorphism may not be associated with obesity and T2DM. These results suggest that, PPAR-γ2 is unlikely a major gene for obesity or T2DM in the study population.

Association of the PPARγ2 Pro12Ala and C1431T Polymorphisms with Type 2 Diabetes and Diabetic Retinopathy in a Sample of Egyptian Patients

Association of the PPARγ2 Pro12Ala and C1431T Polymorphisms with Type 2 Diabetes and Diabetic Retinopathy in a Sample of Egyptian Patients

The combination of UCP3–55CT and PPARγ2Pro12Ala polymorphisms affects BMI and substrate oxidation in two diabetic populations

Background and AimTo evaluate the combined contribution of UCP3–55CT and PPARγ2 Pro12Ala polymorphisms as correlates of BMI, energy expenditure (REE) and substrate oxidation in people with type 2 diabetes. Methods and ResultsTwo independent population with type 2 diabetes were studied: population A, n = 272; population B, n = 269. Based on both UCP3 and PPARγ2 genotypes three groups were created. Carriers of the PPARγ2 Pro12Ala in combination with the CC genotype of UCP3 (ProAla/CC, group 1); carriers of only one of these genotypes (either CC/ProPro or CT-TT/ProAla, group 2); people with neither variants (CT-TT/ProPro, group 3). In both populations BMI (kg/m2) was highest in group 1, intermediate in group 2 and lowest in group 3, independent of energy intake (i.e 35.3 ± 6.7 vs 33.4 ± 5.4 vs 31.8 ± 3, p < 0.02, population A; 32.4 ± 4.2 vs 31.7 ± 3.8 vs 30.1 ± 2.7; p < 0.03, population B). People with the ProAla/CC genotype (group 1) showed similar REE, but lower lipid oxidation (10.9 vs 13.9 g/kg fat free mass/day; p = 0.04) and higher carbohydrate oxidation (23.6 vs 15.6 g/kg fat free mass/day; p = 0.02) than carriers of other genotypes. ConclusionsThe combination of UCP3–55 CC and PPARγ2 Pro12Ala genotypes is associated with significantly higher BMI than other PPARγ2-UCP3 genotype combinations, partly due to a reduced ability in lipids oxidation. The relative importance of these mechanism(s) may be different in non diabetic people.

Association between the PPARγ Pro12Ala polymorphism and risk of gestational diabetes mellitus: a meta-analysis.

The relationship between the Pro12Ala polymorphism of PPARγ and the risk of gestational diabetes mellitus remains unresolved. Here, we attempted to resolve this inconsistency. Case-control studies pertaining to the effect of the Pro12Ala polymorphism in the PPARγ protein and risk of gestational diabetes mellitus were extracted from the HuGE, PubMed, Web of Science, CNKI, and SinoMed databases after an extensive literature search. The studies were statistically analyzed using STATA (v.12.0) software. Twelve case-control studies composed of 2968 GDM cases and 5576 controls that fulfilled the inclusion criteria were included in this meta-analysis. We identified no significant relation between the Pro12Ala polymorphism of PPAR-γ and risk of GDM, when analyzed by the allele [G vs C: odds ratio (OR) = 0.85; 95% confidence interval (CI): 0.71-1.01] and dominant (CG+GG vs CC: OR = 0.86; 95% CI: 0.72-1.03) models. Subgroup analysis by ethnicity revealed that East Asian and Middle Eastern females expressing the A allele showed reduced susceptibility to GDM. Additionally, we observed significant differences between the East Asian, Middle Eastern, and Caucasian females (P = 0.008) with respect to GDM susceptibility. The results of this meta-analysis indicated the influence of ethnicity in determining GDM susceptibility, in the presence of a Pro12Ala polymorphism in PPARγ.

Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis

Background: The aim of this systematic review was to evaluate the relationship between obesity and peroxisome proliferator-activated receptor-gamma (PPARγ) Pro12Ala polymorphism in healthy adults. Summary: Weighted mean differences (WMDs) of body mass index (BMI) were calculated for different inheritance models and subgroups. Fifty-six studies were eligible for inclusion in the meta-analysis. The result shows that the Ala allele of this polymorphism was associated with increased WMD in mean BMI (WMD = 0.29, 95% CI 0.10-0.48, p = 0.003). The Ala carriers were associated with increased WMD in mean BMI values in both genders and in the Caucasian subgroup. The associations were seen among people with higher levels of BMI (BMI ≥35). Message: The Ala allele of the PPARγ Pro12Ala polymorphism in healthy adults was associated with increased BMI under a dominant model of inheritance.

Genotyping of Peroxisome Proliferator-Activated Receptor gamma in Iranian Patients with Helicobacter pylori Infection

Helicobacter pylori (H. pylori) infection as a serious problem in both adults and children can induce chronic gastritis, peptic ulcer disease (PUD), and possibly gastric cancer. The aim of the current study was to survey antibiotic resistance and also to determine influence of PPARγ polymorphism in patients with H. pylori infection. During an 11-month-period, 98 H. pylori isolates were collected from 104 biopsy specimens. In vitro susceptibility of H. pylori isolates to 4 antimicrobial agents metronidazole, clarithromycin, amoxicillin and tetracycline were assessed by quantitative method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PPARγ polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of H. pylori infection in our study was 94.2%. In vitro susceptibility data showed that highest level of resistance was related to metronidazole (66.3%), and the majority of H. pylori isolates were highly susceptible to amoxicillin and tetracycline (94.9% and 96.9%, respectively). Genotypic frequencies were 25.5% for CC (Pro12Pro), 40.8% for GC (Pro12Ala) and 33.7% for GG (Ala12Ala). In our study, CG genotype had highest distributions among infected patients with H. pylori. The study suggests that the PPAR-γ Pro12Ala polymorphism could be evaluated as a potential genetic marker for susceptibility to gastric cancer in the presence of H. pylori infection.

Maternal PPARG Pro12Ala polymorphism is associated with infant's neurodevelopmental outcomes at 18 months of age

BackgroundPeroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, glucose metabolism, anti-inflammatory processes, placental development, and are involved in cognitive functions and neurodegenerative diseases. Polymorphisms in PPAR genes are shown to influence the activity of these receptors. Aims1) To examine the association of PPARG Pro12Ala polymorphism in pregnant women and their offspring on infant's neurodevelopmental outcomes during the first 18months of life; 2) to determine the influence of Pro12Ala polymorphism on fatty acid concentrations in plasma phospholipids and placental tissue. Study design138 mother–infant pairs from the PREOBE observational study were genotyped for PPARG Pro12Ala. Plasma phospholipids and placental fatty acid concentrations were measured at delivery. Infants' neuropsychological assessment at 6 and 18months of age was performed using Bayley III. ResultsThe effect of Pro12Ala on infant's neurodevelopmental outcomes was detected at 18months, but not at 6months of age. 18months old infants born to mothers with wild-type Pro12 genotype had better cognitive (OR=5.11, 95% CI: 1.379–18.96, p=0.015), language (OR=3.41, 95% CI: 1.35–11.24, p=0.044), and motor development scores (OR=4.77, 95% CI: 1.243–18.33, p=0.023) than the Ala allele carriers. Pro12Ala variants did not seem to affect fatty acids concentrations in blood nor in placenta at delivery. ConclusionsInfants born to mothers with Pro12 genotype have better neurodevelopmental outcomes at 18months of age than Ala allele carriers, indicating a long-term transplacental action of PPARγ variants on foetal brain development.

Peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism could be a risk factor for gastric cancer.

Due to the strong inhibitory effects of PPARγ gene on the growth of cancer cells, the role of Pro12Ala polymorphism in PPARγ gene has been extensively investigated in cancer recently. However, the results were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate the PPARγ Pro12Ala polymorphism and gastric cancer susceptibility. Search strategies were conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledge infrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November 01, 2014. The strength of association between PPARγ Pro12Ala polymorphism and gastric cancer risk was assessed by OR with 95%CI. A total of 546 cases and 827 controls in 5 case-control studies were included in this meta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk for gastric cancer when compared with the homozygote CC (odds ratio (OR)=2.31, 95% confidence interval (CI)=1.67- 3.21 for CG+GG vs. CC). In the subgroup analysis by ethnicity, significantly elevated risks were both found in Asians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroup analysis by H. pylori status, a significantly increased risk was identified in H. pylori (+) populations (OR=3.68, 95%CI=2.07-6.52), but not in H. pylori(-) populations (OR=1.17, 95%CI=0.58-2.39). This pooled analysis suggested that the PPARγ Pro12Ala polymorphism could be an independent predictive risk factor for gastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectively designed cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirm the combined effects of PPARγ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk.

Association of the PPARγ2 Pro12Ala polymorphism with increased risk of cardiovascular diseases.

This meta-analysis investigated the correlation between the PPARγ2 Pro12Ala polymorphism and cardiovascular disease (CVD). Electronic database and manual searches were conducted to retrieve studies published relevant to the PPARγ2 Pro12Ala polymorphism and CVD. Rigorous inclusion and exclusion criteria were employed for selection of high-quality patients-control studies. Statistical data analyses on allelic, dominant, homozygous, heterozygous, and recessive inheritance models were performed using the R 3.1.0 and Stata 12.0 software. We enrolled 12 case-control studies consisting of 10,189 patients with CVD [1070 with myocardial infarction (MI), 7849 with coronary artery disease (CAD), and 1270 with acute coronary syndromes (ACS)] and 17,899 controls. The results of meta-analyses revealed that the PPARγ2 Pro12Ala (rs1801282) polymorphism was correlated with a higher risk of CVD under both allelic and dominant models, while no statistical significance was found under homozygous, heterozygous, or recessive models. Subgroup analysis based on disease showed that the PPARγ2 Pro12Ala (rs1801282) polymorphism was correlated with a higher risk of MI under both allelic and dominant models, while no statistical significance was found for association with CAD or ACS under allele or dominant models. Furthermore, under homozygous, heterozygous, and recessive models, the PPARγ2 Pro12Ala (rs1801282) polymorphism had no statistically significant association with MI, CAD, or ACS. The results of this meta-analysis suggest that the PPARγ2 Pro12Ala (rs1801282) polymorphism might be correlated with a higher risk of CVD, particularly MI, and could serve as an important early indicator for CVD.