PPARgamma Gene Research Articles

6913 Clinical Prognosis in Patients with Thyroid Nodules Expressing PPAR-Gamma Gene Fusion on Thyroid FNA Cytology

Abstract Disclosure: R. Hammoudeh: None. E. Morariu: None. A. Wald: Other; Self; Technical consultant to Sonic Healthcare USA.. W.R. Doerfler: None. Y. Linwah: None. M. Nikiforova: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Y.E. Nikiforov: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Background: PPARG rearrangements, typically PAX8-PPARG, are common genetic alterations in follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma (FVPTC). Most tumors appear to be indolent, however distant metastasis has been reported. The aim of this study was to determine the prevalence and type of malignancy in a series of thyroid nodules positive for PAX8 rearrangement in thyroid fine-needle aspiration (FNA) samples. We also aimed to evaluate the impact on patient management, prognosis and outcomes. Methods: Thyroid nodules positive for PAX8 fusion on ThyroSeq v2 and v3 genomic classifier testing of FNA samples from May 2008 to February 2022 were identified. Clinical data was obtained by retrospective chart review. Results: Overall, 44 nodules positive for PAX8/PPARG fusion were identified. None of these nodules expressed additional genetic mutations on molecular testing. Surgical pathology was available for 40 patients, which identified 35 (87.5%) malignant, 3 NIFTP (7.5%), and 2 benign (5%) lesions. In the malignant group, FNA cytology revealed 1 (2.8%) benign, 13 (37.1%) AUS/FLUS, 12 (34.2%) suspicious for SFN/FN, 5 (14.3%) suspicious for PTC and 4 were not classified. In the non-malignant group, FNA cytology revealed 2 (40%) benign, 2 (40%) AUS/FLUS, 1 (20%) SFN/FN. With regards to surgical intervention, 30 (75%) patients had total thyroidectomy and 10 (25%) underwent lobectomy, of which 8 were followed by completion thyroidectomy. Among the malignant and non-malignant groups, there was no difference in sex (82.8% vs 100% female, p=1), age (43.6 vs 50.2 years, p=0.2), or tumor size on surgical pathology (3.26 vs 4 cm, p=0.23). In the malignant group, histology showed 30 (85.7%) FVPTC, 2 (5.7%) conventional PTC, 2 (5.7%) follicular carcinoma and 1 (2.9%) solid variant PTC. Of the FVPTC group, 9 had oncocytic cell features, 3 focal solid patterns, and 1 showed focal solid growth and progression to poorly differentiated thyroid carcinoma. Only 1 showed lymphatic invasion, 10 showed angioinvasion. Following the ATA thyroid cancer risk stratification, 23 (65.7%%) had low risk, 9 (25.7%) intermediate risk and 3 (8.6%) high risk. 18 patients in the malignant group underwent RAI ablation. Average follow up for the malignant nodules was 49.7 months (0-170). 1 had suspected recurrence on thyroid ultrasound after a year. No evidence of distant metastasis was documented. Conclusions: The majority of thyroid nodules with PAX8/PPARG rearrangement found on FNA were cancers, predominantly follicular variant PTC, and some were benign or NIFTP. The majority were low risk, but intermediate and high-risk cancers with more aggressive histology, angioinvasion, and poorly differentiated cancer were also identified. While only one recurrence was identified on short follow-up, longer follow-up duration is required for better understanding the behavior of these tumors. Presentation: 6/3/2024

Deficiency of PPAR Gamma in Bone Marrow Stromal Cells Does Not Prevent High-Fat Diet-Induced Bone Deterioration in Mice

ObjectivesObesity is detrimental to bone health in humans and in high-fat diet-induced obese animals. Bone marrow osteoblasts and adipocytes are derived from a common mesenchymal stem cell and have a reciprocal relationship. Peroxisome proliferator-activated receptor gamma (PPAR gamma), a regulator for adipocyte differentiation, may be a potential target for reducing obesity and increasing bone mass. This study tested the hypothesis that bone-specific PPAR gamma conditional knockout (cKO), via deletion of PPAR gamma gene from bone marrow stromal cells (BMSC) using Osterix 1 (Osx1)-Cre, would prevent high-fat diet-induced bone deterioration in mice. MethodsPPAR gamma cKO (PPAR gammafl/fl: Osx1–Cre) and floxed littermate control (PPAR gammafl/fl Osx1-P-Cre-) mice at 6-wk-old were randomly assigned to 4 groups (n = 12/group, 6 male and 6 female) and fed ad libitum either a normal-fat purified diet (NF, 3.85 kcal/g, 10% energy as fat) or a high-fat diet (HF, 4.73 kcal/g) for 6 mo. Bone structure, body composition, and serum bone-related cytokines were measured. ResultsCompared to the NF diet, the HF diet increased body mass and fat mass (P < 0.05) but not lean mass. The HF diet also decreased tibial and lumbar vertebrae trabecular volume/total volume (BV/TV) and bone mineral density (BMD) in both control and PPAR gamma cKO mice. PPAR gamma cKO mice had lower body fat mass and lean mass than control mice. PPAR gamma cKO mice had greater tibial trabecular BV/TV, trabecular number, connectivity density, and BMD and lower structure model index, compared to control mice. None of trabecular bone parameters at 2nd lumbar vertebrae was affected by genotype. PPAR gamma cKO mice had lower cortical medullary area, compared to control mice. PPAR gamma cKO mice had lower (P < 0.01) serum concentration of leptin and higher (P < 0.05) concentration of osteocalcin, compared with control mice. ConclusionsThese data indicate that PPAR gamma has site-specific impact on bone structure in mice and that knockout PPAR gamma in BMSC increased bone mass in tibia likely through increased osteoblastogenesis. However, PPAR gamma disruption in BMSC did not prevent high-fat diet-induced bone deterioration in mice. Funding SourcesUSDA-ARS #3062-51,000-053-00D.

Regulation of PPARgamma2 Gene Expression by PcG AND pRb Family Proteins in the Course of Adipogenic Differentation of Mesenchymal Stem Cells

Regulation of PPARgamma2 Gene Expression by PcG AND pRb Family Proteins in the Course of Adipogenic Differentation of Mesenchymal Stem Cells

Peroxisome Proliferator-Activated Receptor Gamma Pro12Ala/C161T Genotypes and Risky Haplotype Altering Risk of Breast Cancer: A Turkish Case-Control Study.

Breast cancer (BC) has a high incidence rate among women worldwide, and the mechanisms and etiology of this disease are not yet fully understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor that plays important roles in energy metabolism and cellular differentiation, is also suggested to be effective in cancer development. However, the results of studies investigating the cancer association with PPARgamma are inconsistent, creating a need for further investigation of the effects of this transcription factor on BC risk. We have examined the Pro12Ala-(rs1801282) and C161T-(rs3856806) polymorphisms of the PPARgamma gene in Turkish patients with BC in this case-control study. A total of 95 women diagnosed with BC as cases and 119 controls were genotyped for PPARgamma polymorphisms by polymerase chain reaction and restriction fragment length polymorphism techniques. The ProPro genotype and T161 allele were associated with an increased risk of BC comparing with the Ala12 allele and CC161 genotype, respectively (p < 0.001). The multivariate regression analysis confirmed that the ProPro genotype (p < 0.011), T161 allele (p < 0.001), smoking (p = 0.019), and advanced age (> 60years) (p = 0.007) are risk factors for breast cancer. We also found that the PPARgamma Pro12Ala and C161T polymorphisms were in linkage disequilibrium (D':0.511, r2:0.099). It was determined that carrying ProPro-T161 risky PPARgamma haplotype was associated with a higher risk of BC compared to protective Ala12-CC161 haplotype (p < 0.01, OR:7.797, 95% CI:3.521-17.263). We concluded that PPARgamma Pro12Ala and C161T polymorphisms are associated with increased BC risk, and ProPro-T161 risky haplotype, which is in linkage disequilibrium, increases this effect.

Association of PPAR Gamma Gene Polymorphism; C161T with Diabetes in Population of Pakistan

Diabetes mellitus is defined by an abnormally high blood glucose level. Insulin resistance, beta-cell dysfunction, and endogenous insulin production are all symptoms of type 2 diabetes, also known as Non-Insulin Dependent Diabetes Mellitus (NIDDM). With 38 million people, Asian Indians have a higher prevalence of diabetes. Many single nucleotide polymorphisms in the Peroxisome Proliferator Activated Receptor Gamma (PPAR-) gene play a role in the development of diabetes, either directly or indirectly. On exon 6 of the PPAR gamma gene, a silent mutation at position 161 convert the C allele into T allele. We obtained 926 individual samples from the local population, 500 were controls (fasting blood sugar &lt; 99 mg/dL, random blood sugar &lt; 126 mg/dL) and 426 were diabetes patients (fasting blood sugar &gt; 99 mg/dL, random blood sugar &gt; 126 mg/dL). In serum analysis lipid profiling was done that include TG, TC, LDL-C, HDL-C, and leptin. DNA was isolated and quantified; ARMS (amplification-refractory mutation system) PCR technique was used subsequently. The genotypic frequencies for CC, CT, and TT in diabetes patients are 66.66%, 20%, and 13.33%, respectively. Normal persons had genotype frequencies of 48.78%, 39.02%, and 12.19% for CC, CT, and TT, respectively. Minor allele frequency did not differ considerably between patients and controls (p-0.273). The patients and controls had considerably varied anthropometric and biochemical characteristics. To our knowledge, this is the first attempt to investigate such an association in the local population.

Pro12Ala polymorphism in PPAR-γ gene of impaired glucose tolerance subjects in Bangladeshi population

Pro12Ala polymorphism in PPAR-gamma (PPAR-γ) gene is associated obesity and hyperglycemia in some races, but controversy exists for other races. In this study, 113 impaired glucose tolerance (IGT) and 113 healthy control subjects were recruited. Wild type (CC), heterozygous (CG), and homozygous (GG) variants of Pro16Ala polymorphism of PPAR-γ (rs1801282) were analyzed using Chi-square test, and the polymorphism was found significantly (p=0.05, Χ2=5.875) associated with IGT subjects. Allele frequency also shows significant association with IGT subjects in the Chi-square test (p=0.026, Χ2=2.248). When the waist-hip ratio was reanalyzed according to genotype variation, the waist-hip ratio was found significantly higher among subjects with heterozygous and homozygous variants of pro16Ala polymorphism. Therefore, our study concluded that PPAR-γ P12A variants might be associated with impaired glucose tolerance. It is also documented that higher waist to hip ratio in IGT subjects may associate with heterozygous (CG) and homozygous (GG) variants of Pro12Ala mutation in the PPAR-γ gene.&#x0D; Journal of Bangladesh Academy of Sciences, Vol. 44, No. 2, 179-189, 2020

Leonotis Leonurus improves the crosstalk between peripheral tissues both in vivo and in vitro

Ethnopharmacological relevanceUnravelling the anti-diabetic mechanism of action of L. leonurus at adipose, liver, muscle and pancreatic level. AimsTo investigate the mechanism of action of an organic extract of L. leonurus and marrubiin at the gene level in adipose, liver and muscle tissues of an obese rat model and in a co-culture model. Materials and methodsObese Wistar rats were fed a cafeteria diet for eight weeks, treated with an extract of L. Leonurus, marrubiin, sulfonylurea and aspirin for two weeks and the level of gene expression of selected markers were investigated across different tissues. The effects mediated by the different treatments were investigated in co-culture cell models involving 3T3-L1 (fat), Chang (liver), C2C12 (muscle) and INS-1 (pancreatic) cells under both normal and hyperglycemic conditions. ResultsL. leonurus extract mediated a significant increase in PPAR gamma, glucokinase, FAS and UCP2 gene expression in adipose tissue, whilst the opposite was observed in the liver. At the muscle level, a significant increase in FAS gene expression was observed relative to the obese control rats. Furthermore, the extract as well as marrubiin, modulated improvements in the adipokine profile. The co-culture models showed that the effect mediated by the extract was dependent on, the tissue type as well as the glycemic conditions. ConclusionsL. Leonurus extract as well as marrubiin exhibit anti-diabetic properties where the mechanism of action is mainly at the adipose tissue level. The increase in expression of the genes of interest mentioned above potentially play a protective role towards the liver and possibly towards the muscle tissues as well.

Octyl gallate induces hepatic steatosis in HepG2 cells through the regulation of SREBP-1c and PPAR-gamma gene expression.

Octyl gallate (OG) is an antioxidant commonly used in food, although there is no definition of its acceptable daily intake. There are reports in vitro and in vivo showing that food additives and drugs can alter lipid metabolism. Lipid droplet accumulation in hepatic cells is one of the main findings in the unregulated lipid metabolism and is strongly related to the development of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of OG on lipid metabolism in the hepatocellular carcinoma cell line (HepG2). The results have shown, for the first time, that treatment with OG increased the overall amount of lipids, the triglyceride concentration, the lipid droplet area, and SREBP-1c and PPAR-γ gene expression. Taken together, the findings indicate that OG induces lipid droplet accumulation in HepG2 cells through the regulation of SREBP-1c and PPAR-γ gene expression without involving mTOR/S6K1 and may contribute to NAFLD when used as a food additive.

Genetic Background of Hypertension in Connective Tissue Diseases.

Peroxisome proliferator-activated receptors (PPAR gamma-2) and beta-3-adrenergic receptors (ADRB3) are involved in the risk of hypertension. But their exact role in blood pressure modulation in patients with connective tissue diseases (CTD) is still not well defined. In this study, 104 patients with CTD and 103 gender- and age-matched controls were genotyped for Pro12Ala and C1431T polymorphisms of the PPAR gamma-2 gene and Trp64Arg polymorphism of the ADRB gene. Anthropometric and biochemical measurements were evaluated, followed by genotyping using TaqMan® SNP genotyping assays and polymerase chain reaction-restriction fragment length polymorphism. The prevalence of analyzed genotypes and alleles was comparable between patients with CTD and the control group, as well as hypertensive and normotensive subjects. Patients with CTD have lower body fat and higher body water amount, serum glucose, and triglyceride (TG) levels. Hypertensive subjects are older and have higher body mass, BMI, waist circumference (WC), body water content, glucose, and TG concentration. The multivariate analysis revealed that hypertensive subjects with Ala12/X or Trp64Trp have higher body mass and WC when compared to normotensive subjects. Trp64Trp polymorphism was also characterized by a higher TG level, while T1431/X subjects had higher WC. The presence of CTD, visceral fat distribution, and increased age are the predictors of hypertension development. Hypertensive patients with CTD and Trp64Trp polymorphism have an increased risk of visceral obesity development and metabolic complications, which in turn affects the value of blood pressure. In addition, either Ala12/X or T1431/X predicts the visceral body fat distribution in hypertensive subjects.

Effect of thiazolidinediones on dislipidemia in patients with metabolic syndrome depending on the gene PPAR-gamma rs1801282 polymorphism

Background. To evaluate the effect of thiazolidinediones on lipid spectrum of blood in patients with metabolic syndrome depending on gene polymorphism rs1801282.&#x0D; Materials and methods. The study included 109 patients with newly diagnosed metabolic syndrome. All subjects in the study underwent general clinical, laboratory methods, presence of polymorphism rs1801282 of the PPAR-gamma gene was also determined. All patients were recommended to keep a diet, increase physical activity and receiving pioglitazone 30 mg per day for the period of 3 months.&#x0D; Results.During therapy with pioglitazone it was noted that the degree of reduction of triglycerides was more pronounced in patients with IGT carrying rs1801282 -1.2 (-1.7; -1.1) versus -0.2 (-0.4; 0.0) in patients with wild genotype (p &lt; 0.001) as well as in patients with type 2 diabetes, carries of polymorphic allele -1.3 (-1.6; -1.2) versus -0.2 (-0.3; 0.0) in patients with wild genotype (p &lt; 0.001).&#x0D; Conclusion. As a result of administering pioglitazone, an improvement in the lipid spectrum of the examined patients was noted. The maximum degree of reduction of triglycerides was observed in patients carrying rs1801282 polymorphic allele compared with the wild genotype.

Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice.

Aerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session. mRNA was determined by RT-qPCR, protein levels by immunoblot and 14C-cholesterol efflux determined in macrophages. AET did not change body weight, plasma cholesterol, triglycerides, glucose and CETP activity. In macrophages, at time 0 h, a higher expression of genes that encode PPAR gamma, ABCA-1 and a lower expression of MCP-1 and IL-10, was observed in T as compared to S. After 48 h, lower expressions of MCP-1 and PPAR gamma genes were observed in T mice. Increase in ABCA-1, SR-BI and IL-6 and decrease of LOX-1, MCP-1, TNF and IL-10 gene expression was observed in the aorta of T compared to S mice (0 h) and LOX-1 and MCP-1 remained diminished after 48 h. The protein level of MCP-1 and SR-BI in the aortic arch was unchanged in T animals after 48 h as compared to S, but LOX-1 was reduced confirming data of gene expression. The apo A-I and the HDL2 mediated-cholesterol efflux (8 and 24 h) were not different between T and S animals. In the presence of CETP, AET positively influences gene expression in the arterial wall and macrophages of CETP-tg mice contributing to the RCT and prevention of atherosclerosis. These changes were perceptible immediately after the exercise session and were influenced by the presence of CETP although independent of changes in its activity. Reductions in gene and protein expression of LOX-1 were parallel and reflect the ability of exercise training in reducing the uptake of modified LDL by the arterial wall macrophages.

PPARgamma-2 and ADRB3 polymorphisms in connective tissue diseases and lipid disorders.

BackgroundThe aim of the research genetic study was to investigate the association between variants (C1431T and Pro12Ala) of the peroxisome proliferator-activated receptor (PPARgamma-2) gene, Trp64Arg polymorphism of the beta-3-adrenergic receptor gene and lipid profile in Polish population including group of 103 patients with connective tissue disease (CTD) and 103 sex-and age-matched controls in context of statin use.MethodsAnthropometric and biochemical parameters were measured by routine methods, followed by genotyping (TagMan® Genotyping Assays, PCR-restriction fragment length polymorphism analysis). Nearly 30% of CTD patients used statins and 10% of the control group.ResultsAlthough there were no differences between alleles and genotypes prevalence between CTD vs control groups, interesting lipid-gene associations were noted in this study. A higher level of triglycerides (TAG) and TAG/high-density lipoprotein (HDL) ratios was observed in CTD patients compared to controls. Similar differences were noted in CTD and control groups without statin treatment. Atherogenic markers: the atherogenic index of plasma, TAG/HDL and low-density lipoprotein/HDL ratio were low in the analyzed groups. Of the six analyzed polymorphisms, the Pro12Pro or C14131C or Trp64Trp genotypes were related to higher TAG and TAG/HDL ratios in patients with CTD; however, the highest TAG values were observed in the presence of the Trp64Trp genotype.ConclusionLipid disorders were present in both groups independent of statin treatment (mixed dyslipidemia and hypercholesterolemia were observed in the CTD and control groups, respectively). The risk of dyslipidemia increases with age. The presence of Pro12Pro, C14131C and Trp64Trp genotypes is related to higher TAG level in CTDs, and of these the Trp64Trp variant most reliably predicts hypertriglyceridemia.

Polymorphisms in PPARG and APOE: relationships with lipid profile of adolescents with cardiovascular risk factors

BackgroundCardiovascular diseases constitute the main death cause worldwide resulting from a combination of genetic and lifestyle factors, and the prevalence among younger individuals has increased. It is important to early identify changes in lipid profile and the influence of genetic variations in specific genes on the individual patterns of lipid profile. Thus, the aim of this study was to verify the relationship of polymorphisms in PPAR-gamma gene (PPARG − rs1801282 − Pro12Ala) and in apolipoprotein E gene (APOE − rs429358 + rs7412, determinants of the APOE2, APOE3, or APOE4 genotypes) with lipid profile of adolescents under cardiovascular risk factors.MethodsThis was a cross-sectional study with 115 adolescents aged 10–19 years, which presented cardiovascular risk factors. The students were evaluated regarding socioeconomic, anthropometric, biochemical, genetic, and dietetic variables. Student’s t test or Mann-Whitney test were applied to the analysis of the genotypes. Multiple linear regression analysis was performed to determine the variables that most influenced the lipid profile.ResultsAdolescents carrying PPARG Ala allele showed higher serum triglycerides (p = 0.0423) and very low-density lipoprotein (p = 0.0410) levels when compared to those carrying the wild genotype. For the APOE polymorphism, it was observed a trend of higher triglycerides (p = 0.0712) and very low-density lipoprotein (p = 0.0758) levels in the adolescents carrying the E4 allele when compared to those who did not carry this allele.ConclusionThe polymorphisms PPARG rs1801282 and APOE rs429358 + rs7412 seem to be related to the development of lipid profile alterations in adolescents.

Association of PPAR gamma gene expression with dietary intake of fat and oil among non-diabetic subjects

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Dietary intake of linoleic, linolenic, oleic, and arachidonic acid PPAR-gamma gene expression in visceral and subcutaneous adipose tissue among healthy subjects

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Impact of the PPAR gamma-2 gene polymorphisms on the metabolic state of postmenopausal women.

The relationship Pro12Ala (rs1801282) and C1431T (rs3856806) polymorphisms of PPAR gamma-2 with glucose and lipid metabolism is not clear after menopause. We investigated the impact of the Pro12Ala and C1431T silent substitution in the 6th exon in PPAR gamma-2 gene on nutritional and metabolic status in 271 postmenopausal women (122 lean and 149 obese). The general linear model (GLM) approach to the two-way analysis of variance (ANOVA) was used to infer the interactions between the analysed genotypes. The frequency of the Pro-T haplotype was higher in obese than in lean women (p less than 0.0349). In the analysed GLM models according to obesity status, the C1431C genotype was related to a lower glucose concentration (beta=-0.2103) in lean women, and to higher folliculotropic hormone FSH levels (beta=0.1985) and lower waist circumferences (beta=-0.1511) in obese women. The influence of C1431C was present regardless of the occurrence of the Pro12Ala polymorphism. The co-existence of the C1431C and Pro12Pro genotypes was related to lower values for triceps skinfold thickness compared those for the T1241/X and Ala12/X polymorphisms (beta=-0.1425). The presence of C1431C decreased the differences between triceps values that were determined by Pro or Ala allele. In conclusion, C1431T polymorphism seems to have a more essential influence on anthropometric and biochemical parameters than is the case with Pro12Ala polymorphism.

Peroxisome proliferator activated receptor gamma polymorphism Pro12Ala in polycystic ovary syndrome (PCOS) of South Indian Population

Abstract Objective To investigate the frequency of Pro12Ala polymorphism in PPAR gamma gene among PCOS of South Indian Population. Understanding this polymorphism may help us in better diagnosis prevention and therapeutic approaches towards management of PCOS. Method A total of 75 women with the diagnosis of PCOS and 75 healthy controls were included in this study. The Pro12Ala variant in the PPAR gamma gene was analysed by PCR-RFLP. Results Genotypic frequencies for PPAR gamma gene Pro12Ala polymorphism showed the frequency of Pro/Pro genotypes was 77% in PCOS and 81% in controls. The odds ratio was 0.71 (95% CI 0.31–1.63) and 2.66 (95% CI 0.21–32.9) and alleles expressed 0.87 (95% CI 0.42–1.79). Regarding hormone levels, there were significant differences between PCOS and non PCOS. Conclusion PPARγ2 gene Pro12Ala polymorphism was supposed to be susceptible genes in PCOS. The present study demonstrated that there is a statistical difference between the distributions of PPAR gamma Pro12Ala polymorphism in South Indian Population.

Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study.

Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone. The study was done as a hospital based pilot project in 30 patients with type 2 diabetes mellitus, on treatment with sulfonylurea or metformin but without adequate glycaemic control. They were started on pioglitazone as add on therapy for a period of 12 weeks. The participants were categorized as responders and non-responders based on the change in HbA1C level after 12 weeks. Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. Logistic regression analysis was done to evaluate the associations between age, baseline body weight, BMI, waist circumference, waist-hip ratio and Pro12Ala variants with the response to pioglitazone. The p-value< 0.05 was considered significant. The frequency distributions of PPAR gamma genotypes were 80% for Pro/Pro and 20% for Pro/Ala in the study population. Among the study participants, 30% were non-responders and 70% responders to pioglitazone. A significantly higher frequency of the polymorphism was detected in the responders (p=0.005) compared to non-responders group. Our study suggests that there is a potential association between Pro12Ala polymorphism and glycaemic response to pioglitazone.

PPAR gamma2 gene polymorphism (Pro 12 Ala) in acne and its severity

PPAR gamma2 gene polymorphism (Pro 12 Ala) in acne and its severity

Estimation of peroxisome proliferators – activated receptor γ gene expression in inflammatory skin diseases: atopic dermatitis and psoriasis

Introduction: Peroxisome proliferators- activated receptors (PPARs) represent a major research target for the understanding and treatment of many skin diseases, such as benign epidermal tumors, psoriasis and atopic dermatitis. Aim: Estimate and analyze the PPAR gamma expression and its pathological role in psoriasis and atopic dermatitis. Materials and Methods: Fifteen patients with atopic dermatitis, fifteen patients with psoriasis and twenty apparently healthy subjects as controls,were included in the current study. We estimate the PPARgamma gene expression in the lesional skin of atopic and psoriatic patients and control, by quantitative real-time RT-PCR. Results: Our data showed a significant decreased PPARgamma expression in lesional skin of atopic dermatitis patients and psoriatic patients (P value<0.001) compared to the control group, and the decrease was more marked in the psoriatic patients (P value<0.001). Conclusion: Abberent PPAR γ expression has an important role in the pathogenesis of psoriasis and atopic dermatitis through the affection of cell proliferation, differentiation and inflammation.