Thyroglobuline Gene Polymorphisms in Autoimmune Thyroid Diseases and Detection of the Association Between HLA-DR3 and Common Thyroglobuline Variants

Bu Tez Afyon Kocatepe Üniversitesi Bilimsel Arastırma Projeleri Koordinasyon Birimi Tarafından 08.Tıp.23 Proje Numarası ile DesteklenmistirOtoimmün Tiroid Hastalıkları (OTH), genetik ve çevresel faktörlerin etkilesimi sonucu gelisen kompleks bir hastalık grubudur ve günümüze kadar, farklı teknikler kullanılarak, OTH ile iliskili duyarlılık genleri tanımlanmıstır. nsan lökosit antijenlerini (HLA) kodlayan genlerin, diger otoimmün hastalıklarda oldugu gibi, OTH ile iliskili oldugu bilinmekte ve özellikle Graves hastalıgında (GH) HLA-DR3 sıklıgına isaret edilmektedir. Tiroid spesifik genlerle iliskili olarak ise, 8q24 lokusunda yer alan tiroglobulin (TG) geninin, OTH ile iliskili bulunan tek tiroid spesifik gen oldugu ifade edilmektedir. Çalısmamızda, TG geni E10SNP24, E10SNP158, E12SNP, E21SNP ve E33SNP polimorfizmlerinin, PCR-RFLP teknigi kullanılarak, GH, Hasimato tiroiditi (HT) ve saglıklı kontrollerdeki dagılımı incelenmis; GH ve kontrol gruplarında, PCR-SSP yöntemiyle HLA-DR3 varlıgı arastırılmıstır. Çalısmamızda ayrıca, TG geni E10SNP24, E10SNP158, E12SNP, E21SNP ve E33SNP polimorfizmleri ile HLA-DR3 iliskisi incelenmisir. Çalısmamızın sonucunda, E33SNP TT genotipini tasımayan bireylerde OTH riskinin arttıgı belirlenmistir. Ayrıca, E12SNP AG genotipini tasımayan bireylerde GH riskinin arttıgı; E12SNP AG genotipini tasımayan bireyler ve E12SNP GG genotipine sahip bireylerin GH riskinin, HT hastalıgı riskinden daha yüksek oldugu görülmüstür. Ancak, E12SNP24, E12SNP158 ve E21SNP polimorfimleri ile OTH arasında anlamlı bir iliski bulunamamıstır. Çalısmamızda, HLA-DR3 ile E10SNP24, E10SNP158, E12SNP, E21SNP ve E33SNP polimorfizmlerinin birlikteliginin GH’ndaki etkisine iliskin anlamlı bir bulguya ulasılamamıstır. Sonuç olarak toplumumuzda, E33SNP TT genotipinin OTH ile iliskili oldugu, E12SNP AG genotipinin GH ile iliskili oldugu ve E12SNP AG ve E12SNP GG genotiplerinin GH ile HT hastalıgı risk oranlarının degerlendirilmesinde önem tasıdıkları görülmektedir. Ancak, TG gen polimorfizmleri ile HLA-DR3 birlikteliginin GH ile iliskisi hakkında, daha kapsamlı ve ileri düzeyde çalısmalara ihtiyaç duyuldugu sonucuna varılmıstır.Autoimmune thyroid disease (AITD) are a group of complex diseases which are caused by the interaction between genetic and enviromental factors and up to the present, susceptibility genes responsible to development AITD are identified by using various tecniques. As can be seen other autoimmune diseases, it is known that the association between genes that are coding Human Leukocyte Antigens (HLA) and AITD and especially it is indicated the frequency of HLA-DR3 in Graves’ disease (GD). Relating to thyroid spesific genes, it is implied that, thyroglobulin (TG) gene that is located 8q24 locus is the first gene for AITD. In our study, we investigated the distributions of E10SNP24, E10SNP158, E21SNP, E12SNP and E33SNP polymorphisms that are located in the TG gene in GD, Hashimato tiroiditis (HT) and healthy controls by using PCR-RFLP technique. We also determinated the existence of HLA-DR3 in GD and healthy control groups by using PCR-SSP method and researched the association between E10SNP24, E10SNP158, E21SNP, E12SNP and E33SNP polymorphisms of TG gene and HLADR3. In accordance with the results, we found that, the risk in the development of AITD was increased in individuals who were not carrier of E33SNP TT genotype. It is also found that, the risk in the development of GD was increased in individuals who were not carrier of E12SNP AG genotype. The risk ratio of the development of GD was found higher than HT in individuals who were not carrier E12SNP AG genotype and individuals who were carrier of E12SNP GG genotype. However, there was no evidence in the association between E10SNP24, E10SNP158, E21SNP polimorphisms and AITD. We couldn’t observed any significant result about the effect of E10SNP24, E10SNP158, E12SNP, E21SNP and E33SNP polymorphisms in combination with HLA-DR, in the development of GD. As the result of this study, we concluded that E33SNP TT genotype is associated with AITD, E12SNP AG genotype is associated with GD and E12SNP AG and GG genotype are important in the comparision of the risk ratio of GD and HT. However, more extensive and advanced studies are needed about the association between GD and polymorphisms of TG gene in commination with HLADR3