PPAR-gamma2 Pro12Ala polymorphism in the population of obese and non-obese men of the city of Wroclaw.

INTRODUCTION: The aim of this study was to examine the association of Pro12Ala PPARgamma2 polymorphism with anthropometric and biochemical parameters defining the risk for the development of metabolic syndrome in a healthy population of men. MATERIAL AND METHODS: The study group consisted of 176 healthy men, aged 25-65 years (average 54.16 years). Polymorphisms of the PPAR-g gene (Pro12Ala, Ala12Ala, Pro12Pro) were explored using the PCR-RFLP method. Plasma glucose, insulin, total cholesterol, LDL, HDL and TG were measured using commercially available kits. RESULTS: The genotypic distribution of the Pro12Ala polymorphism was as follows: Pro/Ala 69.8% (n = 123), Ala/Ala 28.4% (n = 50) and Pro/Pro 1.8% (n = 3). The Pro12Ala and Ala12Ala subjects did not differ in any of the measured variables. The non-obese (BMI < 30 kg/m(2), n = 117) and obese subpopulations (BMI > 30 kg/m(2), n = 56) did not significantly differ in the distribution of the genotypes. In the nonobese subpopulation, the homozygous Ala12 carriers (n = 38, 32.4%) had higher systolic blood pressure, plasma triglycerides, insulin levels and HOMA-IR. CONCLUSIONS: We conclude that despite the high frequency of the Ala allele at the PPAR-gamma2 gene in our population of Polish men, the Ala12 allele does not appear to improve insulin sensitivity or have an influence on the occurrence of obesity. It remains to be explained by larger studies if this polymorphism carries any risk of the development of metabolic abnormalities in non-obese men.

Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome.

INTRODUCTION: It was found that vitamin D may have a direct effect on adipocyte differentiation and metabolism and might be involved in the glucose regulation of insulin secretion, as suggested from the discovery of a nuclear localization of 1,25-(OH)(2)D(3) in pancreatic islets. In recent years, several polymorphisms in the VDR gene which are able to alter the activity of VDR protein have been described. The BsmI and FokI polymorphisms were described in relation to obesity and type 2 diabetes. The aim of the study was to find whether there are associations between BsmI and FokI polymorphisms and anthropometric (BMI, WHR, BP) and biochemical parameters describing metabolic syndrome. MATERIALS AND METHODS: Studied were 176 randomly selected men aged 25-65 years (mean: 51.99 years) with a mean BMI of 28.06 kg/m(2). Two polymorphisms of the VDR gene (FokI and BsmI) were explored using the PCR-RFLP method. Serum glucose, insulin, total cholesterol, LDL, HDL, and TG were measured using commercially available kits. RESULTS: It was found that BB carriers tend to have higher BMI (29.00 +/- 3.74 versus 26.81 +/- 3.76, p = 0.024) and waist circumference (101.79 +/- 10.59 versus 96.23 +/- 10.35, p = 0.014) compared with the bb genotypes. Similarly, FF and Ff carriers had higher fasting insulin levels than the ff genotypes (12.30 +/- 10.26 versus 9.76 +/- 5.88, p = 0.001 and 9.76 +/- 5.88 vs. 6.35 +/- 2.64, p = 0.008), and lover cHDL levels in comparison to ff genotypes (52.28 +/- 10.02 versus 60.63 +/- 16.58, p = 0.015 and 53.70 +/- 12.03 versus 60.63 +/- 16.58, p = 0.032. Besides these, no significant differences were found. CONCLUSIONS: The BsmI VDR polymorphism seems to influence BMI, while the FokI VDR polymorphism appears to affect insulin sensitivity and serum cHDL level.

[Relationship of beta(3)-adrenergic receptor polymorphism with metabolic syndrome and oxidative stress parameters in postmenopausal women]. / Zwiazek polimorfizmu receptora beta(3)-adrenergicznego z wystepowaniem parametrów zespolu metabolicznego i stresu oksydacyjnego u kobiet po menopauzie.

INTRODUCTION: Some studies indicate, that the Trp(64)/Arg(64) polymorphism of beta(3)-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of our study was evaluation of frequency of this ADRB3 polymorphism and his association with metabolic syndrome parameters and oxidative stress in postmenopausal women. MATERIAL AND METHODS: We performed the study among 94 women, aged 50-60, selected randomly from Wroclaw city population. Estimation of anthropometric parameters, densitometry (total body fat, android and gynoid deposits--using DPX(+) Lunar, USA device) and biochemical estimations such as lipid profile, glucose, insulin, estradiol and FSH serum level (using commercial kits) were carried out. Oxidative stress was estimated by measurement of thiobarbituric-reactive substances (TBARS) serum concentration, using Yagi method, on spectrofluorimeter Perkin-Elmer LS55. Blood for analysis was collected before, direct after and 6 h after the 30-minutes physical test using cycloergometer. ADRB3 genotyping was performed by PCR and mini-sequencing using ABI 310 sequencer (Applied Biosystems). RESULTS: The frequency of Trp(64)/Arg(64) genotype in investigated population was 15.8%. The Arg(64)/Arg(64) genotype had only one woman. Women bearing Trp(64)/Arg(64) genotype showed higher mean serum level of triglycerides and lower serum level of HDL-cholesterol in comparison to women bearing Trp(64)/Trp(64) genotype, however without statistical significance (p > 0.05) (respectively, means +/- SD for triglycerides: 140.3 +/- 64.1 vs. 113.9 +/- 56.2 mg/dl; and for HDL-cholesterol: 60.9 +/- 11.9 vs. 67.0 +/- 16.9 mg/dl). Both groups did not differ in any other investigated anthropometric nor biochemical parameter. CONCLUSIONS: 1. The Trp(64)/Arg(64) polymorphism of beta(3)-adrenergic receptor could be associated with lipid profile disorders observed in metabolic syndrome in postmenopausal women, however it should be explained basing on the study with more included subjects. 2. The Trp(64)/Arg(64 )polymorphism of beta(3)-adrenergic receptor has no influence on oxidative stress intensification after standardized physical effort in postmenopausal women.

Post-exercise oxidative stress and obesity in postmenopausal women: the role of beta3-adrenergic receptor polymorphism.

AIM: Some studies indicate that the Trp64Arg polymorphism in the gene encoding the beta3-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of the present study was to evaluate the frequency of this polymorphism and its relationship with obesity and oxidative stress in postmenopausal women. MATERIAL AND METHODS: We performed the study on 200 women, aged 50-60 years. Estimation of anthropometric parameters and total body fat, android and gynoid fat deposits was carried out using dual-energy X-ray absorptiometry. Oxidative stress was estimated by measurement of thiobarbituric acid-reactive substances (TBARS) in serum. Blood for analysis was collected before, directly after and 6 h after a 30-min physical test on a cycle ergometer. ADRB3 genotyping was performed by polymerase chain reaction. RESULTS: The frequency of Trp64/Arg64 genotype in the investigated population was 12%, and of Trp64/Trp64 was 87%. The Arg64/Arg64 genotype was present in only 1% of women. Women bearing the Trp64/Arg64 genotype did not differ in any measured anthropometric parameters from women bearing the Trp64/Trp64 genotype. Moreover, genotype had no influence on oxidative stress parameters. Likewise, in both groups, mean plasma level of TBARS was increased significantly (p < 0.05) directly after the endurance test and remained elevated 6 h after the test. CONCLUSIONS: The Trp64Arg polymorphism of ADRB3 seems to not be related to obesity in postmenopausal women. Moreover, the Trp64Arg polymorphism has no influence on oxidative stress intensification after standardized physical effort in postmenopausal women.

Effects of oestradiol and oestroprogestin on erythrocyte antioxidative enzyme system activity in postmenopausal women.

OBJECTIVE: Data concerning the relationship between sex steroid hormones and the cellular antioxidative enzyme system are controversial. We investigated the effects of oestradiol deficiency after menopause and the influence of transdermal oestradiol therapy (ET) and hormonal (oestradiol plus medroxyprogesterone) replacement therapy (HT) on erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). GSH and selenium (Se) concentrations were also estimated. Serum lipid peroxide (LPO) levels were measured as an indicator of free-radical production and lipid peroxidation. PATIENTS: The study group consisted of 80 postmenopausal women, divided into two subgroups: 26 women with surgically induced menopause (ET1) and 54 women with physiological menopause (HT1). Forty premenopausal healthy volunteers were controls (C group). RESULTS: LPO was higher in postmenopausal women and decreased after both ET and HT. GSH-Px and GSH were lower in the postmenopausal groups but increased significantly after both types of therapy. Se concentrations did not differ significantly among the groups. CAT activities were similar in all groups and decreased after ET and HT. SOD activities in postmenopausal women were similar to those in the C group and did not change significantly after treatment. CONCLUSIONS: The administration of natural oestrogens to postmenopausal women diminishes oxidative stress and increases antioxidative cell potency.

[Leptin level and the PPARgamma2 Pro12Ala and Pro115Gln polymorphisms in women with functional hyperandrogenism. Preliminary report]. / Poziom leptyny i wystepowanie polimorfizmu Pro12Ala i Pro115Gln genu PPARgamma2 u kobiet z czynnosciowym hiperandrogenizmem. Raport wstepny.

UNLABELLED: Hyperandrogenism is a multifactoral chronic disease, characterised by an androgen excess, often connected with obesity, hirsutism, polycystic ovaries, hyperinsulinemia, insulin resistance and hyperleptynemia. Peroxisome proliferator activated receptors (PPARgamma) are one of the factors influencing insulin sensitivity. As a transcriptional factor it plays a crucial role in the regulation of genes involved in insulin action. The aim of this study was to evaluate the frequency of PPARgamma Pro12Ala and Pro115Gln polymorphisms in hyperandrogenic women. The additional aim was to investigate differences in leptin levels in healthy and FOH (functional ovarian hyperandrogenism) women (non-obese and obese). MATERIAL AND METHODS: we investigated 90 women: 72 healthy women (37 nonobese and 35 obese)--control group, and 18 women with FOH (9 nonobese and 9 obese)--FOH group. We performed anthropological examination: BMI, WHR and total-body densytomery, biochemical and hormonal estimations in the whole group. PPARgamma polymorphism was studied using PCR and RFLP. RESULTS: in the control group Pro12Pro ("wild" type) was observed in 45 women (26 obese and 19 nonobese) - 62.5% of the group. Heterozygosity Pro12Ala was observed in 15 women (20.8%): 4 obese and 11 with BMI < 30 kg/m2, homozygosity Ala12Ala was seen in 12 women (16.6%): 5 obese i 7 nonobese. In FOH group "wild" type was discovered in 9 women (4 obese and 5 nonobese) - 50% of FOH group, heterozygosity Pro12Ala was seen in 5 women (27.7%): 2 obese and 3 with BMI < 30 kg/m2, homozygosityAla12Ala was observed in 4 women (22.2%): 3 obese and in 1 non-obese. Ala allel frequency in control group was 28%. (37% in non-obese and 20% in obese). In FOH group Ala allel frequency was 36% (nonobese - 28%, obese - 44%). In the studied group we did not find Pro115Gln polymorphism. Leptin level in control group was 19.92 +/- 14.3 ng/ml, and in FOH group - 23.41 +/- 19.47 ng/ml. Depending on BMI leptin level in non-obese healthy group was 7.45 +/- 3.76 ng/ml, in non-obese FOH women - 18.33 +/- 16.54 ng/ml, p < 0.005. In obese controls leptin level was 43.6 +/- 17.28 ng/ml, and in obese FOH women - 45.72 +/- 14.89 ng/ml. CONCLUSIONS: Leptin level in non-obese FOH women is significantly higher than in lean healthy controls. This difference was not observed in obese women. However the Pro12Ala polymorphism is quite common; it does not seem to be directly related to the obesity connected with hyperandrogenism. Higher frequency of Ala allele In FOH women compared to healthy controls (36% vs 28%) may at least partially explain the beneficial effect of tiazolidinediones in the treatment of hyperandrogenism.

[Is obesity associated with a polymorphism Pro12Ala and Pro115Gln in PPARgamma gene?]. / Czy istnieje zwiazek miedzy otyloscia a polimorfizmem Pro12Ala i Pro115Gln genu PPARgamma?

UNLABELLED: Gene PPARgamma is one of the pivotal factors that influence adipocyte differentiation. It is transcriptional factor that plays a crucial role in the regulation of genes involved in lipid utilisation and storage as well as insulin action. The aim of this study was to evaluate whether PPARgamma Pro12Ala and Pro115Gln polymorphisms are connected with obesity and its anthropological parameters. MATERIAL AND METHODS: we investigated 93 subjects: 72 women (37 non-obese and 35 obese) and 21 men (8 non-obese and 13 obese). We performed anthropological examination: BMI, WHR and total-body densitometry in the whole group. PPARg polymorphism was studied using PCR and RFLP. RESULTS: Pro12Pro ("wild" type) variant was present in 57 subjects (32 obese and 25 non-obese): 45 women (26 obese and 19 non-obese) and 12 men (6 obese and 6 non-obese). Heterozygosity Pro12Ala was observed in 20 subjects (8 obese and 12 controls): 15 women (4 obese and 11 lean) and 5 men (4 obese). Homozygosity Ala12Ala was discovered in 16 subjects (8 obese and 8 controls): 12 women (5 obese and 7 non-obese) and 4 men (3 obese). Pro115Gln variant was not found in any of the studied subjects. CONCLUSIONS: The frequency Ala allele (pro12Ala and Ala12Ala variant) was 28% in the whole group and 25% in the obese subjects. However the Pro12Ala polymorphism is quite common, it does not seem to be directly connected with onset of obesity. But it is interesting that the Ala allele is more frequent in non-obese women comparing to obese women (33 vs 20%). Reverse tendency was seen in men. Pro12Ala and/or Ala12Ala polymorphism is twice more frequent in obese subjects comparing to non-obese ones (38 vs 19%).

[Is obesity associated with a polymorphism Pro12Ala and Pro115Gln in the PPARgamma gene?]. / Czy istnieje zwiazek miedzy otyloscia a polimorfizmem Pro12Ala i Pro115Gln genu PPARgamma?

UNLABELLED: PPARgamma is one of the pivotal factors that influence adipocyte differentiation. It is transcriptional factor that plays a crucial role in the regulation of genes involved in lipid utilisation and storage as well as insulin action. The objective of this study was to evaluate whether PPARgamma Pro12Ala and Pro115Gln polymorphisms are connected with obesity and its anthropological parameters. MATERIAL AND METHODS: We investigated 93 subjects: 72 women (37 non-obese and 35 obese) and 21 men (8 non-obese and 13 obese). We performed anthropological examination: body mass index (BMI), waist to hip ratio (WHR) and total-body densitometry in the whole group. PPARgamma polymorphism was studied using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: Pro12Pro ("wild" type) variant was present in 57 subjects (32 obese and 25 non-obese): 45 women (26 obese and 19 non-obese) and 12 men (6 obese and 6 non-obese). Heterozygosity Pro12Ala was observed in 20 subjects (8 obese and 12 controls): 15 women (4 obese and 11 lean) and 5 men (4 obese). Homozygosity Ala12Ala was discovered in 16 subjects (8 obese and 8 controls): 12 women (5 obese and 7 non-obese) and 4 men (3 obese). Pro115Gln variant was not found in any of the studied subjects. CONCLUSIONS: The frequency Ala allele (pro12Ala and Ala12Ala variant) was 28% in the whole group and 25% in the obese subjects. However the Pro12Ala polymorphism is quite common, it does not seem to be directly connected with onset of obesity. But it is interesting that the Ala allele is more frequent in non-obese women comparing to obese women (33 vs 20%). Reverse tendency was seen in men. Pro12Ala and/or Ala12Ala polymorphism is twice more frequent in obese subjects comparing to non-obese ones (38 vs 19%).