Association of IL-10 and IL-6 Gene Polymorphisms with Type 2 Diabetes Mellitus among Egyptian Patients

Son yıllarda bazı sitokinlerin insülin duyarlı glikoz alınımı ile ilişkiye girebilme ile birlikte insülin direnci meydana getirebilme yeteneğine sahip olduğu bildirilmiştir. Mısırlı tip 2 diabetli hastalarda L-10–1082 and IL-6–174 genetik poliformizm ilişkisini test etmek için ortalama yaşı 57 olan 69 hasta (31 E ve 38 K) ve sağlıklı 98 kişi Nil deltasından çalışmaya alındı. Kontrol grubu ile karşılaştırıldığında tip 2 diabetli hastalar yüksek oranda L-10–1082 GG genotipe (p<0.001, OR = 11.24), IL-10–1082 G allele (p<0.001, OR = 2.2) ve düşük oranda IL-10–1082 GA genotype (p<0.001, OR = 0.22) sahip olduğu gösterilmiştir. Diğer bir sonuç, IL-6–174 CC genotipi sıklıkla diabetli grupta yüksekti (p<0.001, OR = 5.41), IL-6–174 GC ise düşüktü. IL-6–174 GC genotipinde ise her grupta anlamlı farklılık göstermedi. Diğer bir sonuç ise IL-6–174 CC genotip sıklığı diabetikli hastalarda oldukça yüksekti (p<0.001, OR = 5.41), bunun aksine IL-6–174 GC genotipi anlamlı derecede düşüktü (p=0.005, OR = 0.31). G or C allelic sıklığı her iki grupta aynı idi (p>0.05). IL-10–1082 GG ve IL-6–174 CC genotipi ile ilişkili poliformizm Mısır'lı hastalarda bir risk faktörü olabilir

Association of IL-10 and IL-6 Gene Polymorphisms with Type 2 Diabetes Mellitus among Egyptian Patients

Recent findings indicate that certain cytokines are capable of interfering with insulin sensitive glucose uptake and induce insulin resistance. To test for the association of IL-10&ndash;1082 and IL-6&ndash;174 genetic polymorphisms with type 2 diabetes mellitus in Egyptian patients. Participants included 69 cases with type 2 DM (31 males and 38 females) with a median age of 57 years in addition to 98 healthy unrelated controls from the Nile Delta region, Egypt. Compared to controls, cases with type 2 diabetes mellitus showed a highly significant increase in the frequency of IL-10&ndash;1082 GG genotype (p

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  • Harrison SA. Liver disease in patients with diabetes mel- litus. J Clin Gastroenterol 2006; 40(1): 68-76.
  • Williams textbook of endocrinology. (12th ed. ed.). Philadelphia: Elsevier/Saunders pp. 1371-435.
  • Sullivan PW, Morrato EH, Ghushchyan V, Wyatt HR, Hill JO. Obesity, inactivity, and the prevalence of diabetes and diabetes-related cardiovascular comorbidities in the U.S., 2000-2002. Diabetes Care 2005; 28(7): 1599-603.
  • Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 2004; 27: 813-23.
  • Abdallah AN, Cucchi-Mouillot P, Biteau N, Cassaigne A, Haras D, Iron A. Analysis of the polymorphism of the tumor necrosis factor (TNF) gene and promotor and of circulating TNF-alpha levels in heart transplant patients suffering or not suffering from severe rejection. Eur J Immunogen 1999; 26: 249-55.
  • Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, et al. Cytokine gene polymorphism in human disease: on-line databases. Genes Immunity 1999; 1(1):3-19.
  • Ding Y, Kantarci A, Badwey JA, Hasturk H, Malabanan A, Van Dyke TE. Phosphorylation of pleckstrin increases pro- inflammatory cytokine secretion by mononuclear phago- cytes in diabetes mellitus. J Immunol 2007; 179(1): 647-54.
  • Shiba T, Higashi N, Nishimura Y. Hyperglycemia due to in- sulin resistance caused by interferon-gamma. Diabet Med 1998; 15: 435-6.
  • Short AD, Catchpole B, Kennedy LJ, et al. Analysis of can- didate susceptibility genes in canine diabetes. J Hered 2007; 98(5): 518-25.
  • Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683-765.
  • Donnelly RP, Freeman SL, Hayes MP. Inhibition of IL-10 ex- pression by IFN-gamma up-regulates transcription of TNF- alpha in human monocytes. J Immunol 1995; 155: 1420-7.
  • Ross J A. Dynamics of peripheral circulation B. Electrocardiography and disorders of cardiac rhythm. In West JB (ed.). Best and Taylor’s, Physiological basis of medical practice. 11th edition, 1985; PP: 132-136.
  • Trinder P. Determination of blood glucose using an oxi- dase-peroxidase system with a non-carcinogenic chromo- gen. J Clin Pathol 1969;22(2):158-61.
  • Frier BM, Ashby JP, Nairn IM and Blairs JD. Plasma insulin, C-peptide and glucagons concentration in patients with insulin independent diabetes treated with chlorprop- amide. Diab Metab 1981; 7(1): 45-9.
  • Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model of assessment : insulin resistance and beta-cell function from fasting plasma glu- cose and insulin concentration in man. Diabetologia 1985; 28: 412-9.
  • Kolla VK, Madhavi G, Pulla Reddy B, et al. Association of tumor necrosis factor alpha, interferon gamma and IL-10 gene polymorphisms with peripheral neuropathy in south Indian patients with type 2 DM. Arch Med Res 2009; 40(4): 276-84.
  • Wogensen L, Lee MS, Sarvetnick N. Production of IL-10 by islet cells accelerates immune-mediated destruction of beta cells in non obese diabetic mice. J Exp Med 1994 1;179(4):1379-84.
  • Settin A, Ismail A, El-Magd MA, El-Baz R, Kazamel A. Gene polymorphisms of TNF-alpha-308 (G/A), IL-10(-1082) (G/A), IL-6(-174) (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus. Autoimmunity 2009; 42(1): 50–5
  • Scarpelli D, Cardellini M, Andreozzi F, et al. Varients of the interleukin-10 promotor gene are associated with obesity and insulin resistance but not type 2 diabetes in Caucasian Italian subjects. Diabetes 2006; 55(5): 1529-33.
  • Tsiavou A, Hatziagelaki E, Chaidaroglou A, et al. TNF-α, TGF-beta1, IL-10, IL-6 gene polymorphisms in latent au- toimmune diabetes of adults (LADA) and type 2 diabetes mellitus. J Clin Immunol 2004; 24(6): 591-9.
  • Kubaszek A, Pihlajamaki J, Punnonen K, Karhapää P, Vauhkonen I, Laakso M. The C-174G promoter polymor- phism of the IL-6 gene affects energy expenditure and in- sulin sensitivity. Diabetes 2003; 52: 558-61.
  • Herbert A, Liu C, Karamohamed S, Schiller J, Liu J, Yang Q, et al. The -174 IL-6 GG genotype is associated with a reduced risk of type 2 diabetes mellitus in a family sam- ple from the National Heart, Lung and Blood Institute's Framingham Heart Study. Diabetologia 2005; 48(8):1492-5.
  • Stephens JW, Hurel SJ, Cooper JA, Acharya J, Miller GJ, Humphries SE. A common functional variant in the inter- leukin-6 gene is associated with increased body mass in- dex in subjects with type 2 diabetes mellitus. Mol Genet Metab 2004; 82: 180-6.
  • Qi L, van Dam RM, Meigs JB, Manson JE, Hunter D, Hu FB. Genetic variation in IL6 gene and type 2 diabetes: tagging- SNP haplotype analysis in large-scale case-control study and meta-analysis. Hum Mol Genet 2006; 15(11):1914-20.
  • Vozarova B, Fernandez-Real JM, Knowler WC, Gallart L, Hanson RL, Gruber JD, et al. The interleukin-6 (–174) G/C promotor polymorphism is associated with type 2 dia- betes mellitus in Native American and Caucasians. Hum Genet 2003; 112: 409-13.