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Thursday, 1 February 2018

Monogenic, Polygenic and Multifactorial Obesity in Children: Genetic and Environmental Factors



Obesityis a chronic disease that has increased alarmingly in recent years. It is considered a risk factor for the development of diseases such as type 2 diabetes, cardiovascular diseases, dyslipidemia, and some types of cancer. Two genetic profiles have been described: monogenic obesity, in which a single gene is mutated, usually leading to loss-of-function or haploinsufficiency, and polygenic obesity, which involves several polymorphic genes with complex interactions between genes and environmental factors. In the latter case, the frequency of polymorphisms can be very high, depending on the population analyzed. In both cases, the genes of interest are associated with changes in body composition through different mechanisms, including hyperphagia, energy expenditure, adipocyte differentiation and lipolysis. However, most studies have analyzed genes associated with obesity in other populations, and the results are often inconsistent, so it is important to study the context of obesity, such as genetics, biochemical biomarkers and environmental factors. Environmental factors include physical activity, nutritional status, and an intake of foods rich in fats and carbohydrates that favor obesity in children. In addition, several chemical compounds have been described as potential endocrine disruptors that increase BMI and produce obesity, and some biological agents can alter the homeostasis of adipose tissue. In this review, we analyzed the genetic and environmental factors that influence obesity, particularly in children.

OECD: Organization for Economic Cooperation and Development; BMI: Body Measured Index; LEP: Leptin; LEPR: Leptin Receptor; POMC: Proopiomelanocortin; PCSK1: Prohormone convertase 1/3; MC4R: Melanocortin 4 Receptor; SIM1: Single Minded Homologue 1; GWAS: Genome Wide Association Studies; PPARG: Peroxixome Proliferator-Activated Receptor γ; ADIPOQ: Adiponectin; FTO: Fat-Mass and Obesity Associated Gene; SNP: Single Nucleotide Polymorphism; CED: Chemical Endocrine Disrupters; DDE: Diphenyl-dichloro-Ethylene (DDE); BPA: Bisphenol A.

Obesity is a chronic disease of diverse etiology. In the genetic context, monogenic obesity is associated with loss-of-function mutations in a single gene. These mutations are very rare and are in some cases unique to a patient or several members of a family; in some populations with high rates of consanguinity, the mutations are more frequent. In polygenic obesity, there is an interaction between several polymorphic genes; in this case, the frequency is greater than 1% and varies by the population analyzed. In this type of obesity, the risk that is attributed to each allele is generally small, but the additive effect of several risk alleles can considerably increase susceptibility to obesity. Multifactorial obesity refers the involvement of other environmental factors, or the obesogenic environment.

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