Associations between the components of metabolic syndrome and the polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-γ), the fat mass and obesity-associated (FTO), and the melanocortin-4 receptor (MC4R) genes

Abstract

Introduction: Metabolic syndrome (MetS) is regarded as a set of abnormalities, increasing the risk of serious functioning disorders. It can develop as a result of genetic predisposition.Aim: The aim of this study was to establish associations between MetS-related abnormalities and the PPAR-γ rs1801282, FTO rs9939609, and MC4R rs17782313 polymorphisms.Material and methods: The study involved 425 women aged 45-60 years. The participants were surveyed and subjected to anthropometric, biochemical and genetic analysis.Results:In the recessive inheritance model for the FTO polymorphism, a statistically significant relationship was demonstrated between the A/A genotype and glycemia. The results obtained in the codominant and overdominant models for the PPAR-y polymorphism showed a tendency to statistical significance (the C/G genotype inclined to hypertriglyceridemia), and were statistically significant in the codominant, dominant, and recessive models (the C/C genotype predisposed to increased blood pressure).Conclusions: 1. MetS-related abnormalities can be genetically determined, however only some of these relationships can be demonstrated due to the categorical division of symptoms according to the IDF criteria from 2009. 2. The A/A genotype of the FTO rs9939609 polymorphism increases the risk of hyperglycemia, and the C/C genotype of the PPAR-γ rs1801282 variant entails elevated blood pressure in 45-60-year-old women.

The association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland

“…29 The recent analysis of 425 women from West Pomeranian voivodeship revealed that AA homozygotes of FTO rs9939609 presented a higher risk of fasting hyperglycemia than those with at least 1 T allele, but no associations were found in the case of lipids, blood pressure or waist size. 27 In a study concerning other FTO polymorphism -rs9930506 in 442 Polish adults, there was no link between this genetic variation and lipid disturbances or higher fasting glucose level. 13 Recently, Ślęzak et al presented a study where FTO gene variation was related to single metabolic disturbances in a homogenous male group, but the risk of metabolic syndrome was not increased in risk allele carriers.…”

“…25 A recent association analysis in Poland confirmed the correlation between susceptibility loci in intron 1 of the FTO gene with obesity; however, it did not include the aspect of cardiovascular complications. 26 Other studies conducted in Poland were based on smaller sample sizes 13,27 or included only specific groups, like children with diabetes 28 or women with polycystic ovary syndrome (PCOS). 29 We examined the largest number of subjects from an unselected Polish population for the FTO variation and metabolic syndrome components.…”

Seeking genetic determinants of selected metabolic disorders in women aged 45–60

“…The results were obtained as part of a larger investigation to analyze the influence of a wide array of biological, social, and psychological factors on women's functioning in the peri-and postmenopausal periods. The authors of this study recommend reading their papers on studies of same study sample, aimed at establishing the association between different MetS-related abnormalities and gene polymorphisms [15], and to assess relationships between MetS and the presence of the FTO rs9939609, the MC4R rs17782313, and the PPAR-γ rs1801282 polymorphisms in 45-60-year-old women [16].…”

PPARγ and Its Agonists in Chronic Kidney Disease

“…Besides the wide distribution in adipocytes, adrenal gland, spleen, muscle, etc., PPARc is also widely expressed in vascular endothelial cells and smooth muscle cells and regulates smooth muscle proliferation, migration and apoptosis, inflammation, atherosclerosis, and other pathologic processes [82]. Studies both in vivo and in vitro supported that PPARc plays a vital protective role in cardiovascular disorders.…”

“…Benkirane et al figured out that PPARc might be responsible for the amelioration of vascular remodeling in hypertension, the mechanisms of which may include inhibiting the expression of matrix metalloprotein-9 (MMP-9) and disturbing PI3K and MAPK signaling pathways [87,88]. Recent studies reported that PPARc can regulate BP through renin-angiotensin-aldosterone system (RAAS), which acts as a negative regulator of Ang II receptor 1 transcription via the following pathways: inhibiting the expression of angiotensinogen, inhibiting Ang II activity, and degrading the angiotensin receptor I expression in the VSMCs [21,82]. Clinical researchers have found a significant reduction in blood pressure after the rosiglitazone treatment in type 2 diabetic patients [89].…”