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Investigation of fat mass and obesity associated (FTO) gene polymorphism in Romanian population
Abstract
Obesity is one of major causes of morbidity in human population due to increased rate and to the consequent rise in co-morbidities such as metabolic syndrome diseases (including type 2 diabetes and hypertension). Thus, interventions to decrease its incidence are essential and they may be elaborated based on precise knowledge of the molecular causes of this pathologic state. Genetic polymorphisms in the fat mass and obesity-associated (FTO) gene have been strongly associated with obesity in humans. However, the biological mechanism of the FTO gene polymorphism associations with obesity and its most relevant parameter, body mass index (BMI), remained still not deciphered. Recent research revealed the critical region in this gene, the first intron, comprising the most cited risk polymorphic loci for obesity in Caucasian population. One of these polymorphic loci, FTO rs1421085, which has been considered the most robustly linked with overweight/obesity, became of special interest in this study that referred to a sample of 138 individuals enrolled randomly in a direct-to-consumer nutrigenetic test during 2016-2018. Starting with genotyping FTO rs1421085 in order to estimate the risk C allele frequency this work aimed to evaluate the risk for overweight. Their BMI values however showed an interesting statistical relevance. No significant difference was obtained using one-way ANOVA; instead, the highest BMI values was noted for subjects with CC genotype, and using Student t-test we observed a significant difference (p=0.029), between TT and C/C(T) genotypes. χ² test showed a significantly correlation between the presence of C allele and higher BMI. Fisher’s exact test, indicated an OR=1.48 (odd ratio), and RR=1.32 (relative risk), suggesting that individuals carrying C allele are at the higher risk to have an increased BMI than the TT homozygote individuals. However, consideration of age intervals by alternative, mean statistical approach revealed other correlations. The association between the genotype and the age of the participants was measured and a conclusive positive correlation was found only until age 51, genotype CC showing to be prone to a higher BMI (p-value 0.028691, a statistical significant result at p < 0.05). A biological mechanism is described based on recent literature reports confirming the complex multifactorial (genetic-epigenetic and environmental) aspects of obesity/overweight not only at the genetic and environmental level, but also at the chromatin and functional genomics level.
... With an everchanging lifestyle and increasing food safety issues, coronary heart diseases, diabetes, obesity, hypertension, and several other health conditions are increasing. Obesity is also linked with diabetes, heart diseases etc. [1]. However, as observed by doctors and nutritionists, consumption of a balanced diet having certain components on a regular basis is helpful in reducing the risk of lifestyle disorders. ...
The dietary requirement depends upon various factors such as age, occupation, location, and health condition. With an ever-changing lifestyle and increasing food safety issues, coronary heart diseases, diabetes, obesity, hypertension, and several other health conditions are increasing. However, as observed by doctors and nutritionists, the consumption of certain food items is associated with the prevention of disorders. Bioactive components are the extra nutritional components present in minute quantities in food. They are intensively studied to evaluate their effects on human health. These bioactive compounds differ widely in their chemical structure and function and thus are categorized accordingly. Bioactive lipids can play a crucial role in prevention against the onset of certain disorders. The present paper reviews the different dietary bioactive lipids, the effect of their consumption on health, and challenges in the incorporation of such components into food systems.
A cluster of single nucleotide polymorphisms (SNPs) in the first intron of the fat mass and obesity related (FTO) gene were the first common variants discovered to be associated with body mass index and body fatness. This review summarises what has been later discovered about the biology of FTO drawing together information from both human and animal studies. Subsequent work showed that the 'at risk' alleles of these SNPs are associated with greater food intake and increased hunger/lowered satiety, but are not associated with altered resting energy expenditure or low physical activity in humans. FTO is an FE (II) and 2-oxoglutarate dependent DNA/RNA methylase. Contrasting the impact of the SNPs on energy balance in humans, knocking out or reducing activity of the Fto gene in the mouse resulted in lowered adiposity, elevated energy expenditure with no impact on food intake (but the impact on expenditure is disputed). In contrast, overexpression of the gene in mice led to elevated food intake and adiposity, with no impact on expenditure. In rodents, the Fto gene is widely expressed in the brain including hypotha-lamic nuclei linked to food intake regulation. Since its activity is 2-oxoglutarate dependent it could potentially act as a sensor of citrate acid cycle flux, but this function has been dismissed, and instead it has been suggested to be much more likely to act as an amino acid sensor, linking circulating AAs to the mam-malian target of rapamycin complex 1. This may be fundamental to its role in development but the link to obesity is less clear. It has been recently suggested that although the obesity related SNPs reside in the first intron of FTO, they may not only impact FTO but mediate their obesity effects via nearby genes (notably RPGRIP1L and IRX3).