Peroxisome Proliferator-activated Receptor Gamma Polymorphisms Research Articles

Association of PPARG and PPARGC1 polymorphism with effectiveness of exercise-induced fat mass loss

Aim. Peroxisome proliferator activated receptor gamma (PPARG) and PPARG coactivator 1α (PPARGC1A) is a key regulator of energy metabolism. This study examines the influence of PPARG and PPARGC1A gene polymorphisms on the PPARG expression, obesity risk, lipoprotein profile and effectiveness of the physical activity intervention for improvement of these parameters. Methods. 39 women with BMI>30 kg/m2 participated in the three-months fitness-program and followed a hypocaloric diet (1500 kCal). At the beginning and at the end of the program, the following anthropometric and biochemical parameters were measured: BMI, percentage of total and visceral fat, amount of plasma lipoproteins, cholesterol, and triglycerides. Single nucleotide polymorphisms were identified in PPARG (n=94) and PPARGC1A (n=138) genes. PPARG mRNA expression was measured through reverse transcription PCR. Results. The physical exercise intervention resulted in a significant fat mass loss in all participants (40.3±5.3% before the study vs 36.4±5.7% after the study, P<0.00001). Polymorphisms rs6442311, rs6846769, rs6846769 were associated with lower visceral fat percent, rs6442311 also correlated with PPARG expression. PPARGC1A polymorphisms rs4458444, rs2305681 were associated with plasma lipoproteins, cholesterol, and triglyceride content. Weight loss effectiveness was connected with rs17650401, rs9833097, rs12629751. Conclusions. After correction for multiple comparisons only rs17650401, of PPARGC1A gene was associated with more effective fat mass reduction.
 Keywords: PPARG, obesity, single nucleotide polymorphism, weight loss, exercise intervention.

PPARG Polymorphisms Are Associated with Unexplained Mild Vision Loss in Patients with Type 2 Diabetes Mellitus.

Objectives To investigate whether the presence of peroxisome proliferator-activated receptor gamma (PPARG) gene polymorphisms is associated with unexplained mild visual impairment (UMVI) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 135 T2DM residents with UMVI and 133 with normal vision (NV; best-corrected visual acuity ≥ 20/25 in both eyes) were enrolled. UMVI was defined as best-corrected visual acuity (BCVA) < 20/25 and ≥ 20/63 in both eyes, with no visual impairment-causing diseases found. Four PPARG gene single-nucleotide polymorphisms (SNPs) (rs3856806, rs1801282, rs709158, and rs10865710) were assessed with the HAPLOVIEW 4.0 software to examine the statistical association of PPARG polymorphisms and UMVI in patients with T2DM. Results Four SNPs qualified the Hardy–Weinberg equilibrium (p > 0.05). The frequency of genotype GC at SNP rs10865710 was significantly higher in the UMVI group than in the NV group (p < 0.001; GG + GC versus CC) (OR = 8.94, 95% CI: 4.90–16.31), whereas genotype CC decreased the risk (OR = 0.07, 95% CI: 0.03–0.14). Genotype TT at SNP rs3856806 was strongly associated with UMVI (p < 0.0001, TT + TC versus CC) (OR = 4.74, 95% CI: 2.68–8.54), whereas genotype CC appeared to be protective for UMVI (OR = 0.55, 95% CI: 0.37–0.82). Conclusions Susceptibilities of PPARG variants may lead to differences in PPARG transcription, result in early function loss of retinal photoreceptor cells, and eventually cause UMVI.

PON2 and PPARG polymorphisms as biomarkers of risk for coronary heart disease.

Investigate the correlation between paraoxonase 2 (PON2) Ser311Cys polymorphism as well as the peroxisome proliferator-activated receptor gamma (PPARG)His477His polymorphism and the susceptibility to development of coronary heart diseases (CHD) through a meta-analysis. Odds ratio and the corresponding 95% CI were used to assess the results. We included 7476 CHD patients and 8504 healthy controls. All the statistical analyses were performed by Comprehensive Meta-Analysis software (CMA, version 2.0). The Ser311Cys polymorphism decreased susceptibility in the overall population and Asian population to CHD. The His477His polymorphism has a protective role in the overall population; however, the subgroup analysis by ethnicity suggested that in Asian population, His477His might increase the risk of CHD. These polymorphisms constitute important predictive indicators of CHD susceptibility.

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.

Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population

AimsThe aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptor gamma (PPARG) with type 2 diabetes mellitus (T2DM) risk and additional role of gene-obesity interaction.MethodsFour SNPs were selected for genotyping in the case–control study: rs1805192, rs709158, rs3856806 and rs4684847. Generalized multifactor dimensionality reduction (GMDR) model and logistic regression was used to examine the interaction between SNP and obesity on T2DM, odds ratio (OR) and 95% confident interval (95% CI) were calculated.ResultsT2DM risk was significantly higher in individuals with rs1805192-G allele (p < 0.05). The carriers of G allele of the rs1805192 polymorphism revealed increased T2DM risk than those with CC variants (CG + GG versus CC, adjusted OR (95% CI) 1.76 (1.45–2.06), p < 0.001). T2DM risk was also significantly higher in individuals with rs3856806-T allele (p < 0.05). The carriers of T allele of the rs3856806 polymorphism revealed increased T2DM risk than those with CC variants (CT + TT versus CC, adjusted OR (95% CI) 1.25 (1.17–1.76), p < 0.001). There was a significant two-locus model (p = 0.0107) involving rs1805192 and obesity. Obese subjects with CG or GG genotype have the highest T2DM risk, compared to subjects with CC genotype and normal BMI (OR 2.40, 95% CI 1.68–3.63).ConclusionsOur results support an important association between rs1805192 and rs3856806 minor allele (G allele) of PPARG and increased T2DM risk, the interaction analysis shown a combined effect of G- obesity interaction between rs1805192 and obesity on increased T2DM risk.

Impact of Interaction Between PPAR Alpha and PPAR Gamma on Breast Cancer Risk in the Chinese Han Population

BackgroundSeveral studies have been conducted to investigate the association of the peroxisome proliferator-activated receptor (PPAR) alpha (PPAR A) and PPAR gamma (PPAR G) polymorphism and breast cancer (BC) risk, but the results were inconsistent, and, until now, no study focused on the impact of gene-gene interactions between PPAR A and PPAR G on BC risk; thus, the aim of this study was to investigate the impact of interaction between PPAR A and PPAR G on BC risk in the Chinese Han population. MethodsA total of 862 participants with a mean age of 63.0 ± 15.7 years were selected, including 432 patients with BC and 430 controls. A logistic regression model was used to examine the association between single-nucleotide polymorphisms and BC risk. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the gene-gene interaction. ResultsLogistic regression analysis showed that BC risk was significantly higher in carriers of G allele of rs1800206 polymorphism than those with CC (CG + GG vs. CC) (adjusted OR, 1.50; 95% CI, 1.20-1.93). In addition, we found that BC risk was also significantly higher in carriers of the G allele of the rs1805192 polymorphism than those with the CC genotype (CG + GG vs. CC) (adjusted OR, 1.78; 95% CI, 1.34-2.26). There was a significant gene-gene interaction between rs1805192 and rs1800206. Overall, the 2-locus models had a cross-validation consistency of 10 of 10, and had a testing accuracy of 60.11%. Patients with CG or GG of rs1805192 and CG or GG of rs1800206 genotype have the highest BC risk, compared with patients with CC of rs1805192 and CC of rs1800206 genotype (OR, 2.59; 95% CI, 1.70-3.48, after covariates adjustment for gender, age, age at menarche, number of children, body mass index, and waist circumference). ConclusionsThe minor allele of rs1800206 and rs1805192 and its interaction were associated with increased BC risk.

Case-control study on peroxisome proliferator-activated receptor gamma polymorphism and interaction with HDL on essential hypertension in Chinese Han.

To investigate the association of single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors gamma (PPARG) with essential hypertension (EH) and additional role of gene- high-density lipoprotein cholesterol (HDL) interaction. A total of 1640 patients with EH (806 males, 834 females), with a mean age of 52.5±12.6 years, were selected, including 816 EH patients and 824 controls, who were enrolled from the community. Three SNPs were selected for genotyping in the case-control study: rs10865710, rs709158, rs1805192. Logistic regression model was used to examine the interaction between SNP and HDL on EH, odds ratio (OR) and 95% confidence interval (95% CI) were also calculated. All genotypes were distributed according to Hardy-Weinberg equilibrium in controls. Logistic regression analysis showed an association between genotypes of variants in rs1805192 and decreased EH risk, EH risk was significantly lower in carriers of Ala allele of the rs1805192 polymorphism than those with Pro/Pro (Pro/Ala+ Ala/Ala versus Pro/Pro, adjusted OR (95% CI) =0.65 (0.53-0.83), after covariate adjustment. In addition, the Ala allele of the rs1805192 polymorphism was also associated with diastolic blood pressure (DBP), but not systolic blood pressure (SBP), we also found, by interaction analysis, combined effect of rs1805192 and HDL on EH risk after covariate adjustment. Our results support an important association between rs1805192 minor allele (Ala allele) of PPARG and lower EH risk, the interaction analysis showed a combined effect of Ala- HDL on lower EH risk.

Association of FTO and PPARG polymorphisms with obesity in Portuguese women

PurposeWe evaluated the association between risk of obesity in the Portuguese population and two obesity-related single-nucleotide gene polymorphisms: fat-mass and obesity-associated (FTO) rs9939609 and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282.Patients and methodsA total of 194 Portuguese premenopausal female Caucasians aged between 18 and 50 years (95 with body mass index [BMI] ≥30 g/m2, 99 controls with BMI 18.5–24.9 kg/m2) participated in this study. The association of the single-nucleotide polymorphisms with obesity was determined by odds ratio calculation with 95% confidence intervals.ResultsSignificant differences in allelic expression of FTO rs9939609 (P<0.05) were found between control and case groups, indicating a 2.5-higher risk for obesity in the presence of both risk alleles when comparing the control group with the entire obese group. A fourfold-higher risk was found for subjects with class III obesity compared to those with classes I and II. No significant differences in BMI were found between the control and case groups for PPARG rs1801282 (P>0.05).ConclusionFor the first time, a study involving an adult Portuguese population shows that individuals harboring both risk alleles in the FTO gene locus are at higher risk for obesity, which is in agreement to what has been reported for other European populations.

Association of peroxisome proliferator-activated receptor gamma polymorphisms with inflammatory bowel disease in a Hungarian cohort

Inflammatory bowel disease (IBD) shows increasing incidence in the last few years in Eastern Europe, including Hungary. Since genetic susceptibility of patients plays an important role in the development and pathogenesis of IBD, it is important to identify new susceptibility genes. Peroxisome proliferator-activated receptor gamma (PPARγ) is expressed in the colon and has protective effects against inflammatory processes. Our aim was to examine the association of four polymorphisms of PPARγ in a well-characterized Hungarian IBD cohort. In all, 575 Crohn's disease (CD), 103 ulcerative colitis (UC) patients, and 486 sex- and age-matched controls were examined. Four polymorphisms of PPARγ (rs10865710 [C-681G], rs2067819, rs3892175, and rs1801282 [Pro12Ala]) were genotyped by TaqMan genotyping assays. The Pro12Ala polymorphism showed significant association with CD when the frequencies of the homozygous variants (Pro/Pro vs. Ala/Ala) were compared. The minor Ala/Ala genotype was significantly less frequent in CD patients compared to the controls (odds ratio [OR] = 0.33; 95% confidence interval [CI] = 012-0.94; P = 0.03), suggesting a potential protective effect of the Ala allele. The GAGG haplotype of PPARγ confers a protective effect in CD; however, it is not significant, but in UC it has a protective effect with a significant level (OR = 0.14; 95% CI: 0.05-0.42; P = 3.78 × 10(-5) ), while GAGC increases the risk of UC (OR = 6.70; 95% CI: 3.41-13.17; P = 3.85 × 10(-10) ). In the present study we demonstrated a significant association between PPARγ polymorphisms and the development of CD and UC at single loci level and also in haplotype combinations.

A peroxisome proliferator‐activated receptor gamma (PPARG) polymorphism is associated with zoledronic acid‐related osteonecrosis of the jaw in multiple myeloma patients: analysis by DMET microarray profiling

A peroxisome proliferator‐activated receptor gamma (<i>PPARG</i>) polymorphism is associated with zoledronic acid‐related osteonecrosis of the jaw in multiple myeloma patients: analysis by DMET microarray profiling

PP-083 Determination of peroxisome proliferator-activated receptor-gamma polymorphism with Helicobacter pylori infection in Iran

PP-083 Determination of peroxisome proliferator-activated receptor-gamma polymorphism with Helicobacter pylori infection in Iran

Peroxisome proliferator-activated receptor gamma polymorphism is related to peak bone mass: the JPOS study

We analyzed 1,217 women to examine the effect of peroxisome proliferator-activated receptors gamma (PPARgamma) C161 --> T on bone status. Among 664 premenopausal women, the C161 --> T is associated with low bone mineral density (BMD) at the total hip and femoral neck. Moreover, the odds ratio for osteopenia or osteoporosis at the femoral neck was 1.98 for premenopausal CT/TT genotypes. The impact of PPARgamma on BMD has not been conclusively established. We examined if PPARgamma C161T polymorphism is associated with BMD and its change. We conducted a baseline survey in 1996 and a 10-year follow-up survey, Japanese Population-based Osteoporosis Study, with a sample population representative of Japanese women. Of these, 1,217 participants in the 1996 survey were analyzed cross-sectionally, while longitudinal analysis was performed on 563 women. A P value < 0.0042 (=0.05/12 for three menstrual statuses and four skeletal sites) was considered statistically significant after Bonferroni correction in multiple testing for cross-sectional analysis. The total hip and femoral neck BMDs were significantly higher for CC genotype than for CT/TT genotypes among 664 premenopausal women (P = 0.0020, P = 0.0022, respectively). Compared to the CC genotype, the odds ratio for osteopenia or osteoporosis (T-scores below -1) at the femoral neck was 1.98 for premenopausal CT/TT genotypes with statistical significance (P = 0.0041). Change of BMD at either skeletal site during the follow-up period was not significantly different for either menstrual status. We conclude that the PPARgamma C161T is associated with low peak bone mass.

Characterization of a Novel Polymorphism in PPARG Regulatory Region Associated with Type 2 Diabetes and Diabetic Retinopathy in Italy

Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes—particularly diabetic women with the proliferative retinopathy—were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not.

Peroxisome proliferator‐activated receptor‐gamma Pro12Ala polymorphism, Helicobacter pylori infection and non‐cardia gastric carcinoma in Chinese

Peroxisome proliferator-activated receptor gamma inhibits the growth and induces apoptosis of gastric cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes and colorectal cancer. To study the association between peroxisome proliferator-activated receptor gamma gene polymorphism, Helicobacter pylori infection and gastric cancer in Chinese. One hundred and four consecutive patients with non-cardia gastric adenocarcinoma and 104 matched controls were examined. Peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. The frequency of peroxisome proliferator-activated receptor gamma G (Ala12) allele was significantly higher among cancer patients (19.2%) than in control (8.7%; OR 2.5, 95% CI 1.1-5.8). While H. pylori infection was more prevalent in gastric cancer patients (OR 3.0; 95% CI 1.6-5.7), the combination of peroxisome proliferator-activated receptor gamma G allele and H. pylori infection further increased the risk of gastric cancer (OR 12.8, 95% CI 3.2-50.5). The presence of the Ala12 did not increase the risk of gastric cancer in H. pylori-negative subjects. Our study suggests the potential association between peroxisome proliferator-activated receptor gamma polymorphism and H. pylori infection in the development of non-cardia gastric cancer.