Tip 2 diyabet (T2DM), insülinin tamamen veya kısmi eksikliğine bağlı olarak gelişen ve hiperglisemi ve insülin direnci ile karakterize bir hastalıktır. İnflamasyon, zararlı, yabancı veya yıkıcı etkilere karşı organizmanın doğal savunma yanıtıdır. Son çalışmalar, inflamasyon, insülin direnci ve tip 2 diyabetin patogenezi arasındaki bağlantıyı vurgulamıştır. İnflamazom, inflamasyon üretme potansiyeli olan uyaranları tanıyan ve buna yanıt olarak proinflamatuar sitokinlerin üretimi ve salgılanmasından sorumlu bir süreci yöneten protein kompleksidir. Farklı tipte inflamazom yapıları bulunmakla birlikte tip 2 diyabet, insülin direnci ve obezite ile ilişkisi rapor edilen inflamazom NLRP3 (Nod-like receptor pyrin domain-containing 3) inflamazomdur. Makrofajlarda, NLRP3 inflamasyonu aktive eder ve insülin sinyalini bozar, ve bu hem TNF-bağımlı hem de TNF bağımsız yolaklar vasıtası ile insülinin hedefi olan hücrelerde insülin direncine neden olur. Çalışmamızın amacı NLRP3 geninin rs4925648, rs121908149 ve rs121908152 varyantlarının ilişkisini araştırmaktır. Bu amaçla 100 T2DM hastası ve 100 kontrol bireye ait DNA’lar NLRP3 geni rs4925648, rs121908149, rs121908152 varyantları için Sequenom MassARRAY® sistemi ve İplex GOLD SNP protokolü kullanarak genotiplendirildi ve sonrasında uygun istatistik yöntemler ile değerlendirildi. Çalışmamız sonucunda rs4925648 (p=0.0108), rs121908149, rs121908152 varyantlarına ait genotip frekansları ile T2DM riski arasında istatistiksel olarak anlamlı fark bulunmamıştır. rs4925648 bölgesi için hasta ve kontrol bireylerde polimorfik genotip olan TT genotipine sahip olan birey bulunmazken, bireylerin CC ve CT genotip dağılımlarının benzer düzeyde olduğu tespit edilmiştir. Bununla birlikte rs4925648 varyasyonu için heterozigot ve dominant modeller istatistiksel olarak anlamlıydı (p=0.048). rs121908149 bölgesi için tüm bireyler, atasal genotip olan CC genotpine sahip olarak belirlenmiştir. rs121908152 bölgesinde de tüm bireyler atasal TT genotip olarak sekanslanmıştır. Bu iki varyantın genotipik çeşitlilik göstermesi bu bölgenin korunmuş bir bölge olabileceği şekilde yorumlanabilir. Sonuç olarak, inflamazom yapısında yer alan NLRP3 genine ait rs121908149 ve rs121908152 varyantları Türk toplumunda T2DM riski ile ilişkili bulunmamakla birlikte rs4925648 varyantı tip 2 diyabetle ilişkili bulunmuştur.

Type 2 diabetes (T2DM) is a disease characterized by a complete or partial deficiency of insulin, hyperglycaemia and insulin resistance. Inflammation is the natural defensive response of the organism against any harmful, foreign or destructive effect. Recent studies have emphasized the link between inflammation, insulin resistance and pathogenesis of type 2 diabetes. Inflammasome is a protein complex that recognizes stimulants with the potential to produce inflammation and, in response, processes a process responsible for the production and secretion of proinflammatory cytokines. There are different types of inflammatory structures, but NLRP3 (Nod-like receptor pyrin domain-containing-3) inflammasome has been associated with type 2 diabetes, insulin resistance and obesity. In macrophages, NLRP3 activates inflammation and impairs insulin signaling, causes insulin resistance by TNF-dependent and TNF-independent pathways in cells targeted to insulin. The aim of our study is to investigate the relationship of rs4925648, rs121908149 and rs121908152 variants of the NLRP3 gene. For this purpose, DNA samples isolated from blood samples of 100 T2DM patients and 100 control individuals were genotyped using the Sequenom MassARRAY system and the Iplex GOLD SNP protocol for the NLRP3 rs10925027 and rs4925659 variants and then evaluated with appropriate statistical methods. As a result of our study genotype frequencies of rs4925648 (p=0.108), rs121908149, rs121908152 variants between the risk of T2DM was not statistically significant difference. While there was no individuals with TT genotype which were polymorphic genotypes in the patient and control subjects for rs4925648 site, it was found that CC and CT genotype distributions were similar. But in heterozygous and dominant model rs4925648 site show statistically significant distribution (p=0.048). The all individuals have CC genotype which is ancestral genotype in the rs121908149. Also in the rs121908152 region, all individuals were sequenced as ancestral TT genotype. The genotypic variation of these variants can be interpreted as this region can be a protected region. In conclusion, rs121908149 and rs121908152 variants from the NLRP3 gene in the structure of the inflammasome could not be associated with T2DM risk in patients with Turkish origin while rs4925648 variant was found to be associated with type 2 diabetes.

Having struggled with many famines throughout its historical journey, looking at the effects and consequences Russia fought the most violent struggle with the mass famine that broke out in 1921-1922 and brought terrible experiences to the Soviet people. When looked at the main causes of this famine, which affected a wide geography, it is seen that it stemed from two main factors. The first of the factors considered from a sociological perspective is that the economy of the country, whose main source of income was agriculture and which struggled with extremely important social events such as World War I, the October Revolution of 1917 and the civil war, lost its arable lands to a great extent during this time. Another factor explained in the physiological context is that the amount of rainfall in the first months of the famine year is below the seasonal norms and the amount of water required by the soils is not reached. As a matter of fact, news of famine began to come from various regions of the country as a result of the crop inefficiency brought by the drought. This famine, which increases in severity day by day, causes the population of the villages to flock to the cities irregularly and en masse. This period, during which the central and local governments were desperate for many other sociological problems, finds its most detailed expression in the work of the writer Aleksandr Neverov’s Tashkent, Cıty Of Bread, who personally experienced the process. The writer, who goes to Tashkent to find bread at the beginning of the famine, enriches what he observed in the meantime in his story on an autobiographical basis. This story, which tells the dramatic story of a young boy struggling to overcome the events that happened to him during his journey to Tashkent in order to save his family, is of great importance in terms of bringing to light a mass tragedy in the history of the USSR while succeeding to take its place among the classics of Soviet literature. In this study, in the context of the relationship between history and literature, the story Tashkent, Cıty Of Bread is examined and the social effects of the Soviet Famine of 1921-1922 are revealed.