Özen GÜL ÖZ, Adem DELİGÖNÜL, Tuna GÜLTEN, Mutlu KARKUCAK, Orhan GÖRÜKMEZ, Mustafa Ferhat ÖKSÜZ, Tahsin YAKUT, Soner CANDER, Gökhan OCAKOĞLU

Tip 1 Diyabet (T1D)'li Türk Hastalarda Glutatyon-S-Transferaz (GSTT1 ve GSTM1) Gen Polimorfizmlerinin Araştırılması

Oksidatif stres, tip 1 diyabet (T1D) ve komplikasyonlarının gelişiminde önemli bir rol oynamaktadır Oksidatif stresin zararlı etkilerine karşısavunma sistemlerinden biri de Glutatyon-S-Transferaz (GST)dır. Çalışmamızda, GSTT1 ve GSTM1 gen polimorfizmleri ile T1Dli Türkhastalar arasındaki ilişkiyi araştırmayı amaçladık. Çalışmamıza, T1D tanısı konmuş 71 hasta ile 62 kontrol birey dahil edildi. GSTM1 veGSTT1 gen polimorfizmini değerlendirmek için multiplex PCR yöntemi kullanıldı. İstatistiksel analizde anlamlılık düzeyi p 0.05). Bu sonuçlar GSTT1 ve GSTM1 negatif(null) genotiplerinin T1D ve komplikasyonların gelişimi için katkısının olmadığını göstermektedir fakat daha geniş olgu sayılı çalışmalara ihtiyaç vardır.

Investigation of Glutathione-S-Transferases (GSTT1 and GSTM1) Gene Polymorphisms in Turkish Patients withType 1 Diabetes(T1D)

Oxidative stress plays an important role in the development of type 1 diabetes(T1D) and its complications. Glutathione-S-Transferases(GST) is one of the defense systems against the harmful effects of oxidative stress. In our study, we aimed to investigate the relationshipbetween GSTT1 and GSTM1 gene polymorphisms and Turkish patients with T1D. In our study, 71 patients were diagnosed with T1D and 62control subjects were included. GSTM1 and GSTT1 gene polymorphisms were used to evaluate the multiplex PCR method.In statisticalanalysis, the level of significance was set at p0.05). These results show that GSTT1 and GSTM1-negative (null) genotypes may notcontribute to the development of T1D and its complications but more studies with larger sample size are needed.

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1. Zurawek M, Fichna M, Fichna P, Januszkiewicz D, Nowak J. No evidence for association of the polymorphisms in NLRP1 gene with type 1 diabetes in Poland. Diabetes Res Clin Pract. 2011;92:e49-51.
2. Cucca F, Lampis R, Congia M, et al. A correlation between the relative predisposition of MHC class II alleles to type 1 diabetes and the structure of their proteins. Hum Mol Genet. 2001;10:2025-37.
3. Todd JA. From genome to aetiology in a multifactorial disease, type 1 diabetes. Bioessays. 1999;21:164-74.
4. Mohammadnejad Z, Ghanbari M, Ganjali R, et al. Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population. Mol Biol Rep. 2012;39:831-7.
5. Domínguez C, Ruiz E, Gussinye M, Carrascosa A. Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents. Diabetes Care. 1998 ;21:1736-42.
6. Fujita H, Narita T, Meguro H, et al. No association of glutathi- one S-transferase M1 gene polymorphism with diabetic nephropathy in Japanese type 2 diabetic patients. Ren Fail. 2000;22:479-86
7. Yalin S, Hatungil R, Tamer L, et al. Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus. Cell Biochem Funct. 2007 ;25:509-13.
8. Hayes JD, Strange RC. Glutathione S-transferase polymorp- hisms and their biological consequences. Pharmacology. 2000;61:154-66.
9. Wilce MC, Parker MW. Structure and function of glutathione S-transferases. Biochim Biophys Acta. 1994;1205:1-18.
10. Bekris LM, Shephard C, Peterson M, et al. Glutathione-s- transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset. Autoimmunity. 2005;38:567-75.
11. Zotova EV, Savost'ianov KV, Chistiakov DA, et al. Search for the association of polymorphic markers for genes coding for antioxidant defense enzymes, with development of diabetic polyneuropathies in patients with type 1 diabetes mellitus. Mol Biol (Mosk). 2004;38:244-9.
12. Yang Y, Kao MT, Chang CC, et al. Glutathione S-transferase T1 deletion is a risk factor for developing end-stage renal disea- se in diabetic patients. Int J Mol Med. 2004;14:855-9.
13. Chistiakov DA, Zotova EV, Savost'anov KV, et al. The 262T>C promoter polymorphism of the catalase gene is associ- ated with diabetic neuropathy in type 1 diabetic Russian patients. Diabetes Metab. 2006;32:63-8.
14. Hovnik T, Dolzan V, Bratina NU, Podkraj sek KT, Battelino T. Genetic polymorphisms in genes encoding antioxidant enzymes are associated with diabetic retinopathy in type 1 diabetes. Diabetes Care. 2009;32:2258-62.
15. Abbas A, Delvinquiere K, Lechevrel M, et al. GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population: different pattern of squamous cell carcinoma and adenocarcinoma. World J Gastroenterol. 2004;10:3389-93.
16. Kiran B, Karkucak M, Ozan H, et al. GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer. J Gynecol Oncol. 2010;21:169-73.
17. Lehmann R, Schleicher ED. Molecular mechanism of diabetic nephropathy. Clin Chim Acta. 2000;297:135-44
18. Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes. 1999;48:1-9.
19. Tiwari AK, Prasad P, B K T, et al. Oxidative stress pathway genes and chronic renal insufficiency in Asian Indians with Ty- pe 2 diabetes. J Diabetes Complications. 2009;23:102-11.
20. Wang G, Zhang L, Li Q. Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk in Chinese population. Biochem Biophys Res Commun. 2006;341:310-3.
21. Bid HK, Konwar R, Saxena M, et al. Association of glutathione S-transferase (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north Indian population. J Postgrad Med. 2010;56:176-81.