Görüntüleme
16
İndirme
2
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, 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) 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 rs10925027 and rs4925659 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.
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 rs10925027 and rs4925659 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.
Alan : Sağlık Bilimleri
Dergi Türü : Uluslararası
Makale Detay 
Benzer Makaleler
PDF Görüntüle
Dergi Bilgisi
Eseri Dinleyin
Alıntı Yap
Bu Sayfayı Yazdırın
Paylaş
Mendeley
