Monogenic obesity – current status of molecular genetic research and clinical importance
Authors:
Irena Aldhoon-Hainerová 1,2; Josef Včelák 1; Hana Zamrazilová 1
Authors‘ workplace:
Endokrinologický ústav, Praha
1; Klinika dětí a dorostu 3. LF UK a FNKV, Praha
2
Published in:
Čas. Lék. čes. 2014; 153: 200-206
Category:
Review Articles
Overview
Obesity and its comorbidities represent one of the major health problems worldwide. A positive energy balance due to inappropriate life-style changes plays a key role in the current obesity epidemic. The influence of genetic factors is also significant – several studies concluded that genes contribute to the development of obesity by 40–70%. Genetic variability predisposes an individual to tendency or resistance to increase body weight in obesogenic environment. Polygenic type of inheritance is responsible in most of obese individuals. However, an intensive research of the past 20 years has led to an identification of several genes causing monogenic forms of obesity. To date, several monogenic genes (leptin, leptin receptor, prohormon convertase 1, proopiomelanocortin, melanocortin 4 receptor, single-minded homolog 1, brain-derived neurotrophic factor, neurotrophic tyrosine kinase receptor type 2) that are either involved in the neuronal differentiation of the paraventricular nucleus or in the leptin-melanocortin pathway are known to cause obesity. Mutation carriers apart from severe early onset obesity manifest with additional phenotypic characteristics as adrenal insufficiency, impaired immunity and impaired fertility. This review provides an overview of molecular-genetic and clinical research in the field of monogenic obesities including therapeutical approaches.
Keywords:
monogenic obesity – energy balance regulation – leptin – leptin receptor – proopiomelanocortin – melanocortin receptor – prohormon convertase – single-minded homolog 1 – brain-derived neurotrophic factor – neurotrophic tyrosine kinase receptor type 2
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