scholarly journals The Pro12Ala Polymorphism of PPAR-γGene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guoda Ma ◽  
Haiyang Wang ◽  
Guixi Mo ◽  
Lili Cui ◽  
You Li ◽  
...  
Keyword(s):  
Disease Severity ◽  
Peroxisome Proliferator ◽  
Healthy Controls ◽  
Chinese Han ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Significant Difference ◽  
Ligation Detection Reaction ◽  
Polymerase Chain ◽  
Sepsis Survivors

Peroxisome proliferator-activated receptor-γ(PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γhas been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γand sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γPro12Ala SNP between septic patients and controls (P=0.622for genotype;P=0.629for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P=0.014for allele andP=0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (allP=0.002). In the survivors, the PPAR-γPro12Ala genotype was significantly associated with decreased disease severity and recovery time (allP<0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

scholarly journals A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity

2001 ◽  
pp. 277-282 ◽  
Author(s):  
MM Swarbrick ◽  
CM Chapman ◽  
BM McQuillan ◽  
J Hung ◽  
PL Thompson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Target Genes ◽  
Venous Blood ◽  
Density Lipoprotein ◽  
Ppar Gamma ◽  
Disease Assessment ◽  
Peroxisome Proliferator ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Significant Difference

OBJECTIVE: Peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma 2) is an important regulator of adipose tissue metabolism and insulin sensitivity. The aim of this investigation was to determine whether a PPAR gamma 2 Pro12Ala polymorphism was associated with cardiovascular risk factors (obesity, blood pressure, diabetes and blood lipids) in Western Australian Caucasians (n=663). DESIGN: Subjects were selected from two population studies (the Carotid Ultrasound Disease Assessment Study (CUDAS) and Busselton Population Health Survey) on the basis of body mass index (BMI). 292 obese (BMI > or =30 kg/m) and 371 lean (BMI <25 kg /m) subjects were studied. METHODS: Blood pressure and anthropometric measurements were collected from all participants, as well as a fasting venous blood sample. Biochemical measurements (high-density lipoprotein (HDL)- and low-density lipoprotein-cholesterol, triglycerides) and PPAR gamma 2 Pro12Ala genotype were also determined. RESULTS: Obese Pro/Ala and Ala/Ala subjects had lower levels of HDL-cholesterol (P=0.032) and a trend towards higher levels of triglycerides (P=0.055) compared with obese Pro/Pro subjects. In the obese group, the Ala allele was significantly associated with the presence of combined hyperlipidaemia (odds ratio = 2.33, P=0.042). There was no significant difference in the frequency of the polymorphism between lean and obese groups (P=0.069). No association was observed between Pro12Ala genotype and obesity, blood pressure or diabetes in either group. CONCLUSIONS: Obese carriers of the Pro12Ala polymorphism have a greater risk of developing combined hyperlipidaemia, possibly due to impaired activation of PPAR gamma target genes. The Pro12Ala polymorphism is not directly associated with obesity, hypertension or diabetes in this population.

scholarly journals Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

2017 ◽  
Vol 5 (3) ◽  
pp. 275-280 ◽  
Author(s):  
Moushira Zaki ◽  
Naglaa Hassan ◽  
Hala T. El-Bassyouni ◽  
Sanaa Kamal ◽  
Walaa Basha ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Fasting Blood Glucose ◽  
Metabolic Parameters ◽  
Peroxisome Proliferator ◽  
Pro12ala Polymorphism ◽  
Ovary Syndrome ◽  
Metabolic Complications ◽  
Peroxisome Proliferator Activated Receptor ◽  
Significant Difference

AIM: To investigate the association of peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its effect on the metabolic parameters in PCOS women.METHODS: The study used PCR to identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and 120 age-matched healthy women. All participants were subjected to anthropometry, biochemical and metabolic evaluation.RESULTS: Significant difference in the genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS women and controls (p = 0.03). The frequency of the polymorphic allele Ala was significantly higher in PCOS cases than that in the controls (OR = 2.01, p = 0.01). The carries of the variant allele Ala in PCOS women showed significant higher values in body mass index (BMI), systolic and diastolic blood pressure, waist circumference, waist to hip ratio, sum of skin folds, fasting blood glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol and low-density lipoprotein than non-carriers.CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications.

scholarly journals Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 gene on lipid profile and adipokines levels in obese subjects

2017 ◽  
Vol 20 (1) ◽  
pp. 71-80 ◽  
Author(s):  
E Becer ◽  
A Çırakoğlu
Keyword(s):  
Serum Lipid ◽  
Peroxisome Proliferator ◽  
Model Assessment ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pcr Rflp ◽  
Obese Subjects ◽  
Polymerase Chain ◽  
Lipid Parameters ◽  
Γ2 Gene

Abstract Peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of metabolism, adipokines production and secretion. The aim of this study was to investigate the association between the PPARγ2 gene Pro12Ala polymorphism in obesity in terms of body mass index (BMI), lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), serum lipid, leptin, adiponectin, resistin and chemerin levels. The study included 160 obese and 140 non obese subjects. The Pro12Ala polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum lipid, leptin, adiponectin, resistin and chemerin levels were measured. No association was found between the Pro12Ala polymorphism and BMI. Strikingly, in the study group, obese subjects with the AA genotype had significantly higher triglycerides (p = 0.046) and resistin (p <0.001) levels than those with the wild-type PP and heterozygous PA genotypes. Serum leptin and chemerin levels were significantly associated with Pro-12Ala poymorphism in the obese and non obese groups (p <0.01). In the obese group, subjects with the homozygous AA genotype had significantly lower adiponectin (p = 0.010) activity than the PP genotype. Our results suggest that the PPARγ2 gene Pro12Ala polymorphism has no direct association with obesity but does have significant influences on lipid profiles and adipokines levels.

scholarly journals Exon 6 and 2 Peroxisome Proliferator-Activated Receptor-γ Polymorphisms in Polycystic Ovary Syndrome

2003 ◽  
Vol 88 (12) ◽  
pp. 5887-5892 ◽  
Author(s):  
Francesco Orio ◽  
Giuseppe Matarese ◽  
Sebastiano Di Biase ◽  
Stefano Palomba ◽  
Donato Labella ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Peroxisome Proliferator ◽  
Pro12ala Polymorphism ◽  
Ovary Syndrome ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exon 2 ◽  
Ppar Γ ◽  
Significant Difference ◽  
Shed Light

Abstract Obesity affects about 44% of women with polycystic ovary syndrome (PCOS). Peroxisome proliferator-activated receptor-γ (PPAR-γ) is one of the genes involved in the differentiation of adipose tissue. In an attempt to shed light on the high percentage of obesity in PCOS, we examined polymorphisms at exons 6 and 2 of the PPAR-γ gene in 100 PCOS patients and in 100 healthy controls matched for age and body mass index (BMI). The T allele frequency of exon 6 was significantly higher (P &lt; 0.05) in PCOS patients compared with control women. In addition, the BMI and leptin levels were significantly higher (P &lt; 0.05) in PCOS patients carrying the C→T substitution than in controls. There was no significant difference in leptin levels after normalization for BMI. The Pro12Ala polymorphism at exon 2 was unrelated to BMI and/or leptin levels in PCOS women. In conclusion, the higher frequency of the C→T substitution in exon 6 of the PPAR-γ gene in PCOS women suggests that it plays a role in the complex pathogenetic mechanism of obesity in PCOS, whereas the Pro12Ala polymorphism does not seem to affect BMI in PCOS women.

Enrichment of IGF-1R and PPARγ signalling pathways in orbital inflammatory diseases: steps toward understanding pathogenesis

2021 ◽  
pp. bjophthalmol-2020-318330
Author(s):  
Rohan Verma ◽  
Dongseok Choi ◽  
Allison J Chen ◽  
Christina A Harrington ◽  
David J Wilson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Diseases ◽  
Target Therapy ◽  
Signalling Pathways ◽  
Peroxisome Proliferator ◽  
Healthy Controls ◽  
Gene Expressions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Orbital Inflammation ◽  
Wide Range

BackgroundOrbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy.AimsTo test the hypothesis that shared signalling pathways are activated in different forms of OID.MethodsIn this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls.ResultsAmong the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways.ConclusionsAlthough OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.

scholarly journals Polymorphism and Human Health

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-15 ◽  
Author(s):  
Weimin He
Keyword(s):  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Unsaturated Fatty Acids ◽  
Polycystic Ovary ◽  
Human Subjects ◽  
Saturated Fatty Acids ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor

The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR, Pro12Ala of PPAR2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPAR2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPAR2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPAR2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.

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