Asocijacija promena antropometrijskih i metaboličkih parametara i aktivnosti enzima antioksidativne zaštite sa polimorfizmom LEP G2548A u genu za leptin kod gojaznih osoba u Srbiji

Abstract

Stopa rasta gojaznosti predstavlja glavni javni zdravstveni problem. U Evropi je njena učestalost u opsegu 10-25% kod muškaraca i 10-30% kod žena. Prevalenca gojaznosti je povećana u Srbiji i ona je postala značajan zdravstveni problem kod odraslih u Srbiji: do 54% ispitanika odraslog stanovništva je gojazno. Gojaznost je bolest koja se definiše kao patološka akumulacija telesne masne mase, koja može nastati kao rezultat povećanog unosa energije i smanjene potrošnje energije. Danas se smatra da je genetska predispozicija za nastanak gojaznosti jedan od glavnih faktora rizika za pojedince, ali identifikaciju gena koji su uključeni u nastanak gojaznosti je još uvek teško razjasniti. S obzirom na činjenicu da je koncentracija leptina znatno povećana kod gojaznih osoba, a istovremeno je proporcionalna telesnoj masi, gen leptina (LEP) je procenjivan u odnosu na genetičke varijante koje bi eventualno mogle biti u vezi sa patofiziologijom gojaznosti i njenim komplikacijama. Leptin je hormon protein kodiran genom gojaznosti (ob), a sintetiše ga pretežno belo masno tkivo. Centralni nervni sistem, tačnije jedra hipotalamusa su meta u kojima leptin ispoljava većinu svojih efekata na metabolizam energije. Leptin ostvaruje nekoliko sistemskih efekata kao što: su smanjenje unosa hrane, povećanje energetske potrošnje, kao i smanjenje metaboličke efikasnosti. Pored toga, leptin utiče na širok spektar bioloških funkcija poput metabolizma lipida i glukoze, sintezu glukokortikoida kao i insulina, a postoji sve više dokaza da je leptin uključen i u patogenezu inflamatornih i autoimunih bolesti. Adekvatne masne naslage i koncentracija leptina smanjuju potrebu za unosom hrane, a omogućavaju potrošnju energije putem raznih neuroendokrinih osa i autonomne aktivnosti. Retki sindromi gojaznosti su povezani sa mutacijama LEP gena kod ljudi. Česta genetička varijanta jednog nukleotida u 5 'promotorskom regionu koji se sastoji u supstituciji G u A na nukleotidu (nt) -2548 (LEP G-2548A, -dbSNPID rs7799039) uzvodno od starta transkripcije ATG u promotoru LEP je povezan sa varijacijama koncentracije leptina u plazmi i indeksom telesne mase (BMI) kod gojaznih osoba...

The growth in obesity rates presents a major public health concern. In Europe, its prevalence is within the range of 10–25% in men and 10–30% in women. The prevalence of obesity increased in Serbia and it became a significant public health problem among adults: up to 54% examinees of adult populations were obese. Obesity is a disease defined as abnormal accumulation of body fat mass, which may arise as a result of increased energy intake and decreased energy expenditure. Genetic predisposition to obesity has been reported as a major risk factor for individuals, but identification of the involved genes is still difficult to elucidate. Considering the fact that leptin concentration is significantly increased in obese persons and at the same time is proportional with body weight, the leptin gene (LEP) has been evaluated for polymorphisms that could potentially be related to the pathophysiology of obesity and its complications. Leptin is a protein hormone encoded by the obese (ob) gene, and is synthesized predominantly by white adipose cells. Central nervous system, namely hypothalamic nuclei, is the target where leptin exerts most of its effects on energy metabolism. Leptin has several systemic effects such as decreases food intake, increases energy expenditure, and decreases metabolic efficiency. In addition, leptin has been shown to influence a wide spectrum of biological functions, such as lipid and glucose metabolism, synthesis of glucocorticoids as well as insulin, and there is an increasing evidence that leptin is involved in the pathogenesis of inflammatory, and autoimmune diseases. Adequate fat stores and leptin concentrations decrease the need for food intake however, allow expenditure of energy via a variety of neuroendocrine axes, autonomic outputs and activities. Rare obesity syndromes are associated with mutations of LEP in humans. A common single nucleotide polymorphism within the 5′ promoter region consisting in G to A substitution at nucleotide (nt) -2548 (LEP G-2548A, -dbSNPID rs7799039) upstream of the ATG start site, in LEP promoter has been associated with variations in the concentrations of plasma leptin and body mass index (BMI) in obese individuals. It has been shown that LEP G-2548A polymorphism influences expression and secretion of leptin in adipose tissue...