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

ABSTRACT: 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.

SUBMITTER: Vales-Villamarin C

PROVIDER: S-EPMC8650059 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The objective of this study was to verify the influence of the Pro12Ala polymorphism of the PPARγ2 gene in response of a training program on the body composition. Sixty-nine previously inactive men and women (32.8 ± 8.2 years) were genotyped and underwent a 12-week aerobic (running/walking) training program (3-5 sessions, 40 - 60 min per session, and intensity between the aerobic and anaerobic threshold) (experimental group n = 53) or were part of the control group (n = 16). They were tested for aerobic capacity (ergospirometry), body composition (DXA), abdomen, waist and hip circumferences and nutritional assessment before and 48 h after the experimental protocol. Two-way repeated measures ANOVA test was used to verify possible differences in variables between the experimental vs. control groups or Pro/Pro vs. Pro/Ala groups, and the Chi-squared test was used to verify the distribution of responders and non-responders according to genotype (p < 0.05). Frequencies of 75.5% Pro/Pro (n = 40) and 24.5% Pro/Ala (n = 13) were found, without any occurrence of the recessive homozygote. Body fat reduction was initially confirmed compared to a control group which did not exercise (n = 16; 29.1 ± 8.8 years), so that the exercise group obtained a reduction of -1.3 kg vs. -0.3 kg in the control group (p = 0.03). When they were divided by genotype, there were significant changes in fat mass (-1.3 ± 2.1 kg; p = 0.00), lean mass (0.6 ± 1.5 kg; p = 0.02), fat percentage (-1.3 ± 1.6; p = 0.00), waist circumference (-2.2 ± 2.9 cm; p = 0.00), abdomen circumference (-3.3 ± 3.6 cm; p = 0.00) and hip circumference (-2.7 ± 2.7 cm; p = 0.00) for Pro/Pro genotypes; and fat mass (-1.1 ± 1.7 kg; p = 0.04), fat percentage (-0.9 ± 1.5; p = 0.04), abdomen circumference (-3.9 ± 3.5 cm; p = 0.00) and hip circumference (-1.8 ± 1.8 cm; p = 0.00) for Pro/Ala genotypes, without any group interaction differences. The Chi squared test revealed no differences in the distribution of responders or non-responders according to genotype. It is concluded that an aerobic training program promotes weight loss, but the Pro12Ala polymorphism in the PPARγ2 gene does not influence the variability of aerobic-induced exercise weight loss.

Project description:Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether the intensity of the immune response during diabetes-associated chronic inflammation affects the development and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in devel-opment of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity com-pared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.

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

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