Pediatrik obezitede melanokortin 4 reseptör geni,plazminojen aktivatör inhibitör 1 geni (-675 4g/5g), tümör nekrozis faktör alpha (-308 g/a), yağ asiti bağlama proteini -87 T/C ve interlökin -6 (-174 G/C) gen değişimlerinin önemi ve siRNA yaklaşım ile fonksiyon tayini
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2006
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Biyoteknoloji Enstitüsü
Abstract
Obesity is a complex, multi-factorial chronic disease, frequently associated with cardiovascular risks, hypertriglyceridaemia, low HDL-cholesterol, high blood pressure and the insulin resistance that appears to be central to the pathogenesis of type II diabetes. Obesity occures when the energy in take from foods is over than energy used and balance is break-down (WHO 2000). Obesity Over the last several decades, cases of obesity and Type II diabetes have reached epidemic proportions and threaten to over burden the world?s health care systems. The incidance of obesity seems over 315 million in the world. This effective increase of obesity is also affect Turkey. In our country; 1/3 of women and 1/5 of men are obese (satman i 2001). There is considerable evidence to suggest that, like height, weight is a heritable trait. Traditionally the most favoured model for seperation of the genetic component of variance is based on studies of twins , as monozygotic co- twins share 100% of their genes and dizygotes 50% on average. Overall, data from twin and adoption studies are consistent with a genetic contribution for body mass index of between 60-84%. It is clear that different individuals have a certain genetic propensity to store excessive caloric intake as fat(Maes, Neale et al. 1997). However the role of PAI-1 in adipogenesis is still unknown, circulating PAI-1 levels are elevated at an early stage of impaired glucose tolerance and continue to be elevated as diabetes and metabolic syndrome develop humans. In our study we investigated PAI-1 promoter -675 4G/5G polymorphism in pediatric obese group as a risk factor with 2.8 fold (Berberoglu, Evliyaoglu et al. 2006). And we demonstrated that the 4G/4G genotype increase the PAI-1 promoter activity, PAI 1 increases the differentiation of preadipocytes to adipocytes. In this present studie, IL-6 -174 G/C and FABP4 T/C polymorphisms were investigated as protector gene alternations and TNF-a -308 G/A polymorphism was not significant in our obese group. Tha last gene we focus on was melanocortin 4 receptor gene that in 18 obese patients, 2 different mutations were found. One of these mutations was a new mutation. So that we conclude, Melanocortin 4 receptor gene and plasminogen activator inhibitor-1 genes modulate the obesity and thought to continue focus on these genes with additional studies. Key Words: Plasminogen activator inhibitor-1 (PAI-1), Melanocortin 4 Reseptor gene (MC4R), Tumor Necrosis faktor ?alpha (TNF-a), Interleukin-6 (IL-6), Obesity, Diabetes mellitus
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Biyoteknoloji