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

Year 2013, Volume: 10 Issue: 3, - 2, 01.09.2013

Mohamed Helaly El-sayed Hatata Megahed Abo El-magd Afaf Alsaid İbrahim Abd El-aal Ahmad Settin

Abstract

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-10–1082 and IL-6–174 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-10–1082 GG genotype (p

Keywords

IL-10, IL-6, gene polymorphism, type 2 diabetes, Egypt

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

Abstract

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

Keywords

IL-10, IL-6, gen poliformizmi, tip 2 diabet, Mısır

References

• 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.