Peroxisome Proliferator-activated Receptor Gamma Gene Research Articles

Multi-locus candidate gene polymorphisms and risk of myocardial infarction: a population-based, prospective genetic analysis.

Polymorphisms in candidate genes related to lipid metabolism, thrombosis, hemostasis, cell-matrix adhesion, and inflammation have been suggested clinically useful in risk assessment of cardiovascular disease. We evaluated a panel of 92 candidate gene polymorphisms, using a multiplex polymerase chain reaction-immobilized probe assay amongst 523 individuals who subsequently developed myocardial infarction (MI), and amongst 2092 individuals who remained free of reported cardiovascular disease over a mean follow-up period of 13.2 years. Of the 92 polymorphisms tested, three that we previously reported on were associated with risk of MI, [pro12ala in the peroxisome proliferator activated-receptor gamma gene (odds ratio, OR = 0.75, P = 0.02); thr164ile in the beta-2 adrenergic receptor gene (OR = 0.14, P = 0.007); and ala23thr polymorphism in the eotaxin gene (OR = 1.87, P = 0.01)]. However, when adjusted for the other 89 polymorphisms evaluated, these findings were no longer statistically significant. Further, in contrast to reports from other investigators, we found little evidence for association of a C677T polymorphism in the 5,10-methylenetetrahydrofolate reductase gene, the angiotensin-I-converting enzyme 1 insertion/deletion polymorphism, a 4G/5G polymorphism in the serine/cysteine proteinase inhibitor-clade E-member 1 gene, the factor V Leiden mutation, the G20210A factor II mutation, a -455G>A polymorphism in the beta-fibrinogen gene, the cys112arg/arg158cys apolipoprotein E gene polymorphism, a gly460trp polymorphism in the alpha-adducin gene, and a -629C>A polymorphism in the cholesteryl ester transfer protein gene with risk of MI. After correction for multiple comparisons, the addition of genetic information observed in the present study had little impact on risk prediction models for MI. The present investigation highlights the importance of replication and validation of findings from genetic association studies.

We-P11:231 C161T polymorphism of peroxisome proliferator-activated receptor gamma gene is associated with prognosis of myocardial infarction

U-series dating of coral associated with former shorelines has provided the abscissa of time for diagrams of fluctuation in sea level during, especially, the last 250,000 years. Ordinates of amplitude have been provided by morphostratigraphic detail, by assumptions of rates of uplift, or by 18O values in either littoral deposits or deep-sea sediments. The latter case provides mutual reinforcement of 18O and sea level chronologies.The most complete reference sections come from the Huon peninsula of New Guinea. Twelve separate reef crests have been distinguished and dated: four in the interval 250 ka to 180 ka (core stage 7), seven in the interval 140 ka to 28 ka (core stages 5-4-3), and one in the in-terval 9 ka to 5 ka. Were 230Th/234U dating sufficiently accurate, sea level histories from other parts of the world might be compared to the New Guinea record, even with the identification of individual sea level events. Such, alas, is not the case. At least the following sources of error plague us.Statistical errors in 230Th/234U values are commonly quoted as ± 0.02, but an interlaboratory comparison suggests that ± 0.04 may be a fairer index of precision. This is ± 15 ka at 125 ka, nearly equal to the 17 ka interval between sea level maxima on New Guinea. Thus, indi-vidual samples from other areas cannot be assigned to a specific episode by “closed-system” ages alone. Close correlation must depend upon position in a morphostratigraphic sequence as well.Corals are not ideal closed systems. 230Th ages may be either too old or too young. Concordancy of 230Th and 231Pa ages is the only useful check, but 231Pa/235U is seldom measured.Molluscan data are notoriously unreliable and would not be studied, were we not curious about the extra-tropical seas. Coexisting coral and mollusca can yield identical 230Th ages. More commonly, molluscan ages are significantly younger. Concordant 230Th and 231Pa ages can be as little as 50% of those from coexisting coral. The molluscan systems have been “closed” to loss of daughter products, but “open” to addition of parent U. We are measuring the average age of the parent, which enters molluscan shell after death.Both coral and mollusca may also be “open systems” to which 234U, 230Th, and/or 231Pa have been added in excess of that produced within the shell. In some cases, addition may have been systematic. The S-R model, which allows correction to “concordant” ages, is not demonstrably useful, but alternative models might be developed from sufficient data.There can be no doubt that “dating” the maximum sea level of the last interglacial at 125,000 ± 10,000 years, and confirmation of its wide-spread preservation are achievements of U-series dating. Detailed sea level records of the “last interglacial” (core stage 5), based on local morphostratigraphic evidence, still show conflicts (differences?) which cannot be resolved by U-series dating.

Th-P15:127 Role of malondialdehyde-modified low-density lipoprotein in restenosis

The objectives were to determine the effects of tocopherol on serum concentrations of 8-epi-prostaglandin F2 alpha (isoprostane) and adiponectin, and to determine mRNA expression of peroxisome proliferator-activated receptor gamma (PPARγ), adiponectin (ADIPQ), and related genes in the uterus and placentome of tocopherol-supplemented ewes during late pregnancy.Pregnant ewes were individually given daily oral supplements of 500 mg of alpha-tocopherol (aT; N=6), 1000 mg of gamma-tocopherol (gT; N=7), or placebo (CON; N=5) from 107 to 137 d post breeding. Serum and tissue samples were collected weekly and at the end of the study, respectively. At the end of the study, in the aT, gT and CON groups, serum concentrations were 251.7 ± 12.3, 232.5 ± 6.8, and 285.8 ± 9.4 ηg/μL, respectively, for isoprostane, and were 341.7 ± 9.3, 358.7 ± 11.5, and 305.2 ± 2.8 ηg/μL for adiponectin (significantly different for aT and gT versus CON). The mRNA abundance for PPARγ in the cotyledon and caruncle were similar in aT and gT ewes. The PPARγ, ADIPQ and LEP mRNA expressions were reduced (P < 0.05) in the cotyledon and caruncle in aT versus CON ewes. However, associations of PPARγ mRNA expression with ADIPQ and LEP mRNA expressions were negatively related in cotyledons, positively related in the caruncle, and positively downregulated in the uterus in gT supplemented ewes accounting for CON. The IGF-1 mRNA expression was downregulated in the cotyledon, caruncle and uterus in aT supplemented ewes. Expression of IGF-2 mRNA was upregulated in the cotyledon and caruncle, and downregulated in the uterus in gT supplemented ewes. In conclusion, oral supplementation of tocopherol during late gestation in ewes decreased isoprostane concentrations and increased adiponectin concentrations in the serum, and significantly affected PPARγ- and ADIPQ-related genes in the utero-placental network. Perhaps the pro-angiogenic tocopherol effect in the placental vascular network was via PPARγ-mediated regulation of genes responsible for metabolism of glucose and fatty acid, as well as for angiogenesis.

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.

Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulin-sensitive subjects

We determined the response of selected genes to in vivo insulin in adipose tissue in 21 non-diabetic women. The women were divided into insulin-sensitive and -resistant groups based on their median whole-body insulin sensitivity (8.7+/-0.4 vs 4.2+/-0.3 mg kg(-1) min(-1) for insulin-sensitive vs -resistant group). Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 h of i.v. maintained euglycaemic hyperinsulinaemia. Adipose tissue mRNA concentrations of facilitated glucose transporter, member 1 (SLC2A1, previously known as GLUT1), facilitated glucose transporter, member 4 (SLC2A4, previously known as GLUT4), peroxisome proliferator-activated receptor gamma ( PPARG), peroxisome proliferator-activated receptor gamma co-activator 1alpha (PPARGC1A), 11beta-hydroxysteroid dehydrogenase-1 (HSD11B1), TNF, adiponectin (ADIPOQ), IL6 and the macrophage marker CD68 were measured using real-time PCR. Basal expression of 'insulin-sensitivity genes' SLC2A4 and ADIPOQ was lower while that of 'insulin-resistance genes', HSD11B1 and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. Insulin significantly increased expression of 'insulin-sensitivity genes' SLC2A4, PPARG, PPARGC1A and ADIPOQ in the insulin-sensitive group, while only expression of PPARG and PPARGC1A was increased in the insulin-resistant group. The expression of 'insulin-resistance genes' HSD11B1 and IL6 was increased by insulin in the insulin-resistant group, but insulin failed to increase HSD11B1 expression in the insulin-sensitive group. At 6 h, expression of HSD11B1, TNF and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. IL6 expression increased significantly more in response to insulin in the insulin-resistant than in the insulin-sensitive group. CD68 was overexpressed in the insulin-resistant as compared with the insulin-sensitive group at both 0 and 6 h. These data suggest that genes adversely affecting insulin sensitivity hyperrespond to insulin, while genes enhancing insulin sensitivity hyporespond to insulin in insulin-resistant human adipose tissue in vivo.

Single Nucleotide Polymorphisms on Peroxisome Proliferator-activated Receptor Genes Associated with Fatness Traits in Chicken

The peroxisome proliferator-activated receptors (PPARs) are members of a superfamily of nuclear hormone receptors. Lots of studies in rodents and humans have shown that PPARs were involved in lipid metabolism and adipocyte differentiation. The main objective of this work was to detect the single nucleotide polymorphisms (SNPs) in whole coding regions of peroxisome proliferator-activated receptor alpha (PPAR-α) and gamma (PPAR-γ) genes with approach of single strand conformation polymorphism (SSCP) in the chicken population of Arber Acres broiler, Hyline layer and three Chinese native breeds (Shiqiza, Beijing You, Bai'er). Two SNPs of C1029T and C297T were found in chicken PPAR-α and PPAR-γ genes respectively and each SNP found three genotypes in the experimental populations. The results showed that the distribution frequency of 3 genotypes in Arber Acres broiler, Hyline layer and Chinese native breeds had significant differences on the PPAR-α and PPAR-γ gene respectively (p<0.01). Furthermore, in the PPAR-α gene, the results of least square estimation for genotypes and body composition traits showed the BB genotype birds had higher abdominal fat weight (AFW) and percentage of abdominal fat (AFP) than AA genotype birds (p<0.05). From these we conjecture the PPAR-α and PPAR-γ genes were suffered intensive selection during the long term commercial breeding and the PPAR-α gene may be a major gene or linked to the major genes that impact chicken fat metabolism and the SNPs could be used in molecular assistant selection (MAS) as a genetic marker for the chicken fatness traits. (Asian-Aust. J. Anim. Sci. 2005. Vol 18, No. 9 : 1221-1225)

Genetic polymorphisms in peroxisome proliferator‐activated receptor γ are associated with Type 2 diabetes mellitus and obesity in the Korean population

We examined whether the common polymorphisms of the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene are associated with Type 2 diabetes or obesity in the Korean population. We genotyped two common PPARgamma polymorphisms (Pro12Ala and 161C > T) and examined their association with the clinical phenotypes found in 684 patients with Type 2 diabetes mellitus and 291 non-diabetic control subjects. The 12Ala allele was less frequent in the Type 2 diabetic patients than in the non-diabetic control subjects (0.036 vs. 0.053, P = 0.024). The allele frequencies of the 161C > T polymorphism did not differ between the control and Type 2 diabetic group (0.158 vs. 0.173). In the non-diabetic controls, those with the T allele had lower BMI and fasting serum triglyceride (TG) concentrations than those with the C/C homozygote (22.7 +/- 2.9 vs. 23.8 +/- 3.2 kg/m2, P = 0.002; 1.45 +/- 0.81 vs. 1.65 +/- 0.83 mmol/l, P = 0.03, respectively). The 12Ala-161T haplotype was associated with a decreased risk for Type 2 diabetes (OR = 0.47, P = 0.009), whereas the 12Pro-161T haplotype was associated with lower BMI and lower fasting serum TG (22.5 +/- 2.8 vs. 23.7 +/- 3.2 kg/m2, P = 0.004; 1.41 +/- 0.87 vs. 1.64 +/- 0.79 mmol/l, P = 0.02, respectively). The PPARgamma 12Ala allele was associated with a reduced risk of Type 2 diabetes, whereas the PPARgamma 161T allele was associated with lower BMI and fasting serum TG concentrations in the Korean subjects. The subjects with 12Ala-161T haplotypes had a reduced risk of Type 2 diabetes.

Influence of the C161T but not Pro12Ala polymorphism in the peroxisome proliferator‐activated receptor‐gamma on colorectal cancer in an Indian population

The aim of the present study was to investigate associations between Pro12Ala and C161T polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and colorectal cancer (CRC) risk. We recruited 301 newly diagnosed CRC patients and 291 healthy control subjects at the Madras Cancer Institute in Chennai, India, from 1999 to 2001. Genotypes of the Pro12Ala and C161T polymorphisms were determined using the PCR-RFLP method. After adjustment for age, sex, smoking habit, family history and family income, an increased risk of CRC was observed for the C/T + T/T genotype compared to the C/C genotype of the C161T polymorphism (odds ratio = 1.61, 95% confidence interval: 1.10-2.36), whereas no significant association was found for Pro12Ala (odds ratio = 1.06, 95% confidence interval: 0.70-1.61). Analysis with estimated haplotypes showed a significant difference in haplotype frequencies between cases and controls (chi(2) = 11.62, P = 0.009, d.f. = 3). The relationship between the two polymorphisms and CRC risk was not significantly modified by dietary intake of fish. Although the biological mechanisms of the observed association remain to be elucidated, our findings suggest that the C161T polymorphism of the PPAR-gamma gene is related to risk of CRC. Further research is needed to investigate functional implications of polymorphisms of the PPAR-gamma gene in CRC development.

Genetics of Leptin and Obesity: A HuGE Review

Leptin is an important regulator of the mass of adipose tissue and of body weight; it operates by inhibiting food intake and stimulating energy expenditure. Some polymorphic genes involved in the regulation of leptin-the leptin gene (LEP A19G), the leptin receptor gene (LEPR Q223R, K109R, and K656N), and the peroxisome proliferator-activated receptor-gamma gene (PPARG P12A and C161T)--have been investigated as possible factors associated with obesity. Allelic frequencies of these polymorphisms show ethnic variation. The authors performed a meta-analysis of the available data on the association between these polymorphisms and obesity based on case-control studies. Odds ratios and 95% confidence intervals for obesity associated with leptin polymorphisms were calculated by using both fixed- and random-effects models. Results suggest no evidence of association between the genes under study and obesity. The lack of association could be due to the complex pathogenesis of obesity, which involves a number of genetic and environmental factors. Large studies including testing of multiple genes in both obese and lean subjects, with epidemiologic data on dietary habits in different ethnic groups, are necessary to better understand the role of leptin in regulating weight in human populations.

381: The PRO12ALA Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene and Risk of Colorectal Cancer in a Korean Population

381: The PRO12ALA Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene and Risk of Colorectal Cancer in a Korean Population

Cytokines and Peroxisome Proliferator-Activated Receptor γ Ligand Regulate Phagocytosis by Pancreatic Stellate Cells

Pancreatic stellate cells have been characterized as the major source of extracellular matrix and cytokine production in the pancreas. This study showed that pancreatic stellate cells have a phagocytic function. The morphological features of periacinar phagocytic cells were investigated by immunohistochemically staining serial sections of the pancreas from male WBN/Kob rats and an animal model of acute pancreatitis for glial fibrillary acidic protein and alpha-smooth muscle actin. Pancreatic stellate cells were assayed for phagocytic activity by incubating them with senescent polymorphonuclear neutrophils or fluorescence-labeled latex beads in the presence or absence of cytokines, growth factors, and peroxisome proliferator-activated receptor gamma ligand. The role of CD36 and peroxisome proliferator-activated receptor gamma in phagocytosis was investigated by blocking endogenous CD36 and peroxisome proliferator-activated receptor gamma activity with anti-CD36 antibody and peroxisome proliferator-activated receptor gamma small interfering RNAs, respectively. Phagocytic cells were observed in areas of inflammation, and they were identical to the glial fibrillary acidic protein-positive and alpha-smooth muscle actin-positive cells, thus suggesting that they were pancreatic stellate cells. Aged polymorphonuclear neutrophils were ingested into the cytoplasm of the pancreatic stellate cells. Transforming growth factor beta, tumor necrosis factor alpha, and interleukin 1beta decreased the phagocytic activity of pancreatic stellate cells, whereas troglitazone induced a dose-dependent increase in both phagocytic activity and expression of CD36. Blockade of CD36 reduced troglitazone-induced phagocytosis. Silencing of the peroxisome proliferator-activated receptor gamma gene decreased phagocytosis and expression of CD36. Pancreatic stellate cells act as resident phagocytic cells, and CD36 promotes troglitazone-induced phagocytic activity via peroxisome proliferator-activated receptor gamma transactivation. Because phagocytosis is essential to limit the extent of inflammation, enhancement of phagocytic activity may provide an important approach to the treatment of pancreatic diseases.

The Effect of the Ala12Allele of the Peroxisome Proliferator-Activated Receptor-γ2 Gene on Skeletal Muscle Glucose Uptake Depends on Obesity: A Positron Emission Tomography Study

The Pro(12)Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene is associated with insulin sensitivity. Obesity is a major risk factor for insulin resistance, but the association of the Pro(12)Ala polymorphism with body weight has been controversial. Furthermore, obesity may modulate the effect of this polymorphism on insulin sensitivity. The aim of our study was to investigate the effects of the Pro(12)Ala polymorphism on skeletal muscle and adipose tissue glucose uptake (GU) in nonobese and obese subjects. The design was a cross-sectional study. The rates of GU were investigated in 124 (72 nonobese and 52 obese; body mass index cutoff point, 27 kg/m(2)) healthy subjects with the euglycemic hyperinsulinemic clamp. Skeletal muscle and adipose tissue GU and skeletal muscle perfusion were measured using fluorine-18-labeled fluorodeoxyglucose, [(15)O]H(2)O, and positron emission tomography. The rates of skeletal muscle GU were higher in nonobese subjects carrying the Ala(12) allele than in subjects carrying the Pro(12)Pro genotype (P = 0.004), whereas no differences were found in skeletal muscle perfusion between the groups. In contrast, in obese subjects the rates of skeletal muscle GU did not differ between carriers of the Ala(12) allele and carriers of the Pro(12)Pro genotype. No difference in adipose tissue GU was found in either nonobese or obese subjects according to Pro(12)Ala polymorphism. We conclude that the Pro(12)Ala polymorphism modulates skeletal muscle GU differently in nonobese and obese subjects.

Effect of the peroxisome proliferator-activated receptor-γ C161T polymorphism on lipid profile in Brazilian patients with Type 2 diabetes mellitus

The aim of the present study was to examine the effects of the C161T polymorphism of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene in Brazilian subjects with Type 2 diabetes mellitus (T2DM) and controls residing in Sao Paulo City, Brazil. Genomic DNA was obtained from 207 patients with T2DM and 170 unrelated normoglycemic individuals (CG). Anthropometric data included: body mass index, waist, hip, waist-to-hip ratio; biochemical parameters: fasting plasma glucose, total cholesterol, HDL- and LDL-cholesterol, triglycerides, glycated hemoglobin and insulin. Systolic and diastolic blood pressure was also measured. Screening for mutations in the entire coding region of the PPARgamma gene was carried out by PCR, single strand conformational polymorphism analysis (SSCP) and sequencing. C161T polymorphism was analyzed by PCR-RFLP. The C161T polymorphism was the only variant found in exon 6 of the PPARgamma gene. The frequency of the 161T allele in T2DM (0.10) was similar to that found in CG (0.07, p=0.210). Serum triglycerides (p=0.040), VLDL-cholesterol (p=0.040) and Atherogenic Index of Plasma (AIP; p=0.003) were significantly lower in 161T allele carriers than non-carriers in women of the T2DM group. Our results show that the C161T polymorphism in the PPARgamma gene is not associated with variables related to T2DM or insulin resistance in the Brazilian population. However, a reduction of serum triglycerides and AIP was observed in women with 161T allele of the C161T polymorphism of the PPARgamma gene.

The effects of C161→T polymorphisms in exon 6 of peroxisome proliferator-activated receptor-γ gene on bone mineral metabolism and serum osteoprotegerin levels in healthy middle-aged women

We evaluated the association of different genotypes in C161-->T substitution in exon 6 of peroxisome proliferator-activated receptor-gamma (PPARgamma) gene with bone turnover markers, bone mineral density (BMD), and serum osteoprotegerin (OPG) in female subjects to reveal the role of PPARgamma in bone. In 263 healthy Korean women (mean age 52 years), anthropometric measurements were taken along with measurements of lumbar spine and femoral neck BMD, bone turnover markers, such as alkaline phosphatase, serum calcium, phosphorus, 24-hour urine calcium, phosphorus excretion, and urine deoxypyridinoline. Serum follicular stimulating hormone levels were measured and serum OPG levels were measured with the enzyme-linked immunosorbent assay method. Polymerase chain reaction-restriction fragment length polymorphism was performed. Allele frequencies were 0.804 for the C allele and 0.196 for the T allele. There were no differences in mean age, body mass index, BMD, and bone turnover markers among different genotypes, and the subjects with T alleles had significantly lower serum OPG levels. There were no differences in the prevalence of metabolic bone diseases according to the genotypes. When analyzed according to the menopausal status, only postmenopausal subjects with T alleles showed significantly lower serum OPG levels. The frequencies of C161-->T substitution in exon 6 of the PPARgamma gene in Korean females were similar to other races and women with T alleles showed significantly lower serum OPG levels and it was especially noted for postmenopausal subjects, which supports the possible concurrent association of PPARgamma and OPG with estrogen status in female subjects.

Gly482Ser polymorphism of the peroxisome proliferator-activated receptor-γ coactivator-1 gene might be a risk factor for diabetic retinopathy in Slovene population (Caucasians) with type 2 diabetes and the Pro12Ala polymorphism of thePPARγ gene is not

The peroxisome proliferator-activated receptor-gamma (PPARgamma) gene has been recently associated with type 2 diabetes, obesity and traits depending on VEGF expression (e.g. retinopathy). The PPARgamma gene and its coactivator, the peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1) gene, have been implicated to be involved in glucose uptake and altered lipid oxidation. We therefore hypothesized that the Gly482Ser polymorphism of the PPARGC1 gene and Pro12Ala polymorphism of the PPARgamma gene might confer susceptibility to diabetic retinopathy in type 2 diabetes. The aim of this study was to investigate the association between the Pro12Ala polymorphism in the PPARgamma gene and Gly482Ser polymorphism in the PPARGC1 gene and the development of diabetic retinopathy in the Slovene population (Caucasians) with type 2 diabetes. One hundred and sixty subjects with type 2 diabetes and diabetic retinopathy were compared with 101 diabetic subjects without diabetic retinopathy. Chi-square test was used to compare discrete variables, and continuous clinical data were compared by unpaired students t - test. A significantly higher frequency of the AA genotype of the Gly482Ser polymorphism of the PPARGC1 gene was found in the patients with diabetic retinopathy compared to the patients without diabetic retinopathy (14.4% vs 5.9%; p = 0.035), whereas the Pro12Ala polymorphism of the PPARgamma gene failed to yield an association with diabetic retinopathy. The present study demonstrates that the AA genotype of the Gly482Ser polymorphism in the PPARGC1 gene might be a risk factor for diabetic retinopathy in the Slovene population (Caucasians) with type 2 diabetes (odds ratio 2.7, 95% confidence interval 1.0-6.8), whereas the Pro12Ala polymorphism of the PPARgamma gene failed to confer susceptibility to diabetic retinopathy.

Investigation of a peroxisome proliferator‐activated receptor gamma haplotype effect on meat quality and carcass traits in pigs

Peroxisome proliferator-activated receptor gamma (PPARG) is a key transcription factor that controls adipocyte differentiation and fat deposition in mammals. The primary goal of this study was to investigate PPARG as a candidate gene for meat quality and carcass traits in swine. Part of the PPARG promoter, along with the most 5'-proximal exon of the gene, was amplified by PCR and subsequently screened for polymorphisms by sequencing. A Met59Val substitution was detected in the porcine PPARG gene along with four polymorphisms in the promoter region of the adipose-specific PPARG2. Three of these polymorphisms were chosen for genotyping and tested for association with meat quality, carcass and growth traits, according to the candidate gene approach. More than 1500 animals from different lines and populations were used in the study with records for meat quality and carcass traits. No convincing associations were found between the traits investigated and the PPARG genotypes. It does not appear that variation at the PPARG locus is affecting meat quality, carcass or growth traits in the pig populations studied.

W14.387 The P12A polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene associated premature coronary heart disease and myocardial infarction. (The Ludwigshafen risk and cardiovascular health study)

W14.387 The P12A polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene associated premature coronary heart disease and myocardial infarction. (The Ludwigshafen risk and cardiovascular health study)

W14.387 The P12A polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene associated premature coronary heart disease and myocardial infarction. (The Ludwigshafen risk and cardiovascular health study)

W14.387 The P12A polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene associated premature coronary heart disease and myocardial infarction. (The Ludwigshafen risk and cardiovascular health study)

1121-50 Peroxisome proliferator-activated receptor gamma gene polymorphisms and risk of restenosis after coronary artery stenting in patients with diabetes

1121-50 Peroxisome proliferator-activated receptor gamma gene polymorphisms and risk of restenosis after coronary artery stenting in patients with diabetes

Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus.

Type 2 diabetes mellitus is a complex genetic disease, which results from interactions between multiple genes and environmental factors without any single factor having strong independent effects. This study was done to identify gene to gene interactions which could be associated with the risk of Type 2 diabetes. We genotyped 23 different loci in the 15 candidate genes of Type 2 diabetes in 504 unrelated Type 2 diabetic patients and 133 non-diabetic control subjects. We analysed gene to gene interactions among 23 polymorphic loci using the multifactor-dimensionality reduction (MDR) method, which has been shown to be effective for detecting and characterising gene to gene interactions in case-control studies with relatively small samples. The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor gamma ( PPARgamma) gene. This interaction showed the maximum consistency and minimum prediction error among all gene to gene interaction models evaluated. Moreover, the combination of the UCP2 55 Ala/Val heterozygote and the PPARgamma 161 C/C homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio: 0.51, 95% CI: 0.34 to 0.77, p=0.0016). Using the MDR method, we showed a two-locus interaction between the UCP2 and PPARgamma genes among 23 loci in the candidate genes of Type 2 diabetes. The determination of such genotype combinations contributing to Type 2 diabetes mellitus could provide a new tool for identifying high-risk individuals.