PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPARγ are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain open regarding the effects of PPARγ on traits related to the development of type 2 diabetes. In our study, we have analyzed the relationship of the common variant Pro12Ala in the human PPARγ2 gene with the presence of obesity and with insulin, HOMA and lipid profile in a representative sample of 6-to 8-year-old children free from the confounding factors associated with adults. We found that Ala12Ala genotype was significantly more frequent in females with obesity than in those without obesity, with Ala12Ala carriers having significantly higher weight and body mass index (BMI), however the association disappeared when adjusting by leptin concentrations. The Ala12Ala genotype was associated with significantly higher HDL-cholesterol and apoA-I levels in males but not in females, independently of BMI. In a recessive model, in females, leptin levels appeared higher in Ala12Ala carriers. Although no apparent differences were observed in any sex when analyzing insulin levels and HOMA among genotypes without adjusting, lower insulin levels and lower HOMA appeared associated with Ala12Ala carriers when adjusting for BMI and leptin levels. In summary, our data showed that leptin seems to be having an effect on the association between the PPARγ2 Pro12Ala and BMI. Besides, after controlling for BMI and leptin, a protective effect of the Ala12Ala variant of the PPARγ2 Pro12Ala polymorphism on insulin sensitivity is evident already in prepubertal children.

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. Journal of Bangladesh Academy of Sciences, Vol. 44, No. 2, 179-189, 2020

Relationship of the Pro12Ala Polymorphism on the PPARy2 Gene With the Body Composition of Practitioners of Cyclic Exercises

This study aimed to verify the association between the genotypic of the receptor gene activated by peroxisome proliferators gamma 2 (PPARy2) and the body composition and the specific indicators of adiposity in practitioners physical exercises, considering nutritional intake, age, and training load as influencing factors. It was conducted a cross-sectional study with 335 adults (47.9 ± 12.7 years, 138 men, body mass index/BMI = 27.0 ± 4.9 kg/m2), practitioners of aerobic exercises in cyclical modalities (running, walking and/or cycling, who spent 328.3 ± 193.6 kcal/day on physical training). The genotyping of the Pro12Ala polymorphism was performed using the PCR-RFLP technique and the body composition measured by bioimpedance (InBody 720). Energy expenditure was based on the compendium of physical activities and caloric intake was measured by 24 h recall questionnaire. The higher prevalence was for the Pro/Pro genotype (76.1% vs. 23.9% of Pro/Ala). Pro/Pro genotypic group showed significant higher mean values for body mass (BM) (p < 0.03 for men and p < 0.02 for women) and BMI (p < 0.00 for men and p < 0.02 for women) and %FAT (p < 0.00), waist-hip ratio (WHR) (p < 0.04), and visceral fat (VF) (p < 0.00) only in men compared to Pro/Ala. Higher frequency of Pro/Pro was observed in the category indicating BMI (p < 0.00 for men and p < 0.03 for women), WRH (p < 0.03 for men and p < 0.00 for women), and %FAT (p < 0.03) (in the latter case, only among men. It was also observed that the frequency of distribution of Pro/Ala in the eutrophic category of the BMI remained independent of all influencers, while WHR and %FAT were independent of the training load, but influenced by nutritional intake and age. In women, the frequency of Pro/Ala distribution at the lowest BMI and WHR values remained independent of all confounding variables. It is concluded that the Pro12Ala polymorphism in the PPARy2 gene consistently influences indicators of body composition and adiposity, regardless of the practitioners of physical training, but the relationship needs to be considered according to age and nutritional intake.

Interaction between the dietary indices (DQI, DPI, HEI) and PPAR-γ gene variants on cardiovascular risk factors in a patient with type 2 diabetes mellitus

Background: We investigated the interaction between PPAR-γ Pro12Ala polymorphism and Healthy Eating Index (HEI), Dietary Quality Index-International (DQI-I) and Dietary Phytochemical Index (DPI) on Cardiovascular Disease (CVD) risk factors in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study was conducted on 393 diabetic patients. PPAR-γ Pro12Ala was genotyped by PCR-RFLP method. Biochemical markers including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), superoxide dismutase (SOD), C-reactive protein (CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), isoprostaneF2α (PGF2α) were measured by standard protocol. FFQ was used for dietary indices (DQI, DPI, HEI) calculation. Results: There was no significant relationship between PPAR-γ Pro12Ala polymorphism and CVD risk factors. The rs1801282-DQI interactions were significant on WC (P= 0.01). Thus, C-allele carriers in the higher tertile of DQI had higher WC compared to GG homozygous. Further, an interaction was observed between PPAR rs1801282 polymorphism and DQI on serum IL-18 level (P = 0.03). Besides, a significant rs1801282-DPI interaction was shown on HDL concentration (P Interaction= 0.04), G allele carriers who were in the highest tertile of DPI, had lower HDL. Moreover, there were significant rs1801282-HEI interactions on ghrelin (P= 0.04) in the crude model and serum leptin (P = 0.02) in the adjusted model. Individuals with (CC, CG) genotypes in the higher tertile of HEI, had lower leptin and ghrelin concentration. Conclusions: Higher dietary indices (DQI, DPI, HEI) may affect the relationship between PPAR-γ Pro12Ala polymorphism and waist circumference and ghrelin, leptin, HDL-c, IL-18 concentration in patients with T2DM. To date, studies on this polymorphism have been shown that this gene can interact with diabetes and different nutritional factors. For the first time, this study provides information on the interaction of dietary indices (DQI, DPI, HEI) and PPAR-γ gene which is functionally effective in nutrient metabolism.

Interaction Between the Dietary Indices (DQI, DPI, HEI) and PPAR-γ Gene Variants on Cardiovascular Risk Factors in a Patient With Type 2 Diabetes Mellitus

Background: We investigated the interaction between PPAR-γ Pro12Ala polymorphism and Healthy Eating Index (HEI), Dietary Quality Index-International (DQI-I) and Dietary Phytochemical Index (DPI) on Cardiovascular Disease (CVD) risk factors in patients with type 2 diabetes mellitus (T2DM).Methods: This cross-sectional study was conducted on 393 diabetic patients. PPAR-γ Pro12Ala was genotyped by PCR-RFLP method. Biochemical markers including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), superoxide dismutase (SOD), C-reactive protein (CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), isoprostaneF2α (PGF2α) were measured by standard protocol. FFQ was used for dietary indices (DQI, DPI, HEI) calculation.Results: There was no significant relationship between PPAR-γ Pro12Ala polymorphism and CVD risk factors. The rs1801282-DQI interactions were significant on WC (P= 0.01). Thus, C-allele carriers in the higher tertile of DQI had higher WC compared to GG homozygous. Further, an interaction was observed between PPAR rs1801282 polymorphism and DQI on serum IL-18 level (P = 0.03). Besides, a significant rs1801282-DPI interaction was shown on HDL concentration (P Interaction= 0.04), G allele carriers who were in the highest tertile of DPI, had lower HDL. Moreover, there were significant rs1801282-HEI interactions on ghrelin (P= 0.04) in the crude model and serum leptin (P = 0.02) in the adjusted model. Individuals with (CC, CG) genotypes in the higher tertile of HEI, had lower leptin and ghrelin concentration.Conclusions: Higher dietary indices (DQI, DPI, HEI) may affect the relationship between PPAR-γ Pro12Ala polymorphism and waist circumference and ghrelin, leptin, HDL-c, IL-18 concentration in patients with T2DM.

The common PPARγ2 Pro12Ala polymorphism is associated with an increased risk of coronary artery disease (CAD) in Iranian patients with type 2 diabetes mellitus

Background. Type 2 diabetes (T2DM) is a risk factor for coronary artery disease (CAD) in patients with type 2 diabetes compared with subjects without diabetes. Many studies have been shown that CAD has resulted from the interaction of genetic markers implicated in dyslipidaemia and oxidative stress. The PPARγ gene is considered as a potential candidate gene for the link between diabetes mellitus and CAD in patients with diabetes mellitus. The purpose of the present study was to determine the association of Pro12Ala PPARγ2 polymorphism (rs1801282) with CAD in Iranian patients with T2DM.Methods. We studied 290 unrelated Iranian subjects, including 145 healthy controls and 145 CAD patients with a history of T2DM. Genomic DNA was isolated from peripheral blood, and the PPARγ2 gene mutations were analyzed using the PCR–RFLP technique.Results. Our results revealed a significant difference between the allele frequencies of PPARγ2 Pro12Ala polymorphism between the case and control subjects. However, no significant association was observed between Pro12Ala genotypes and physiologic variables.Conclusion. In summary, it could be concluded that PPARγ2 Pro12Ala polymorphism may be an essential indicator of the increased risk of CAD in diabetic patients among the Iranian population.Trial Registration. This article does not contain any studies with human participants by any of the authors.