Afaf ELSAİD, A. Mohamed HELALY, El-Sayed Z. HATATA, Osama FOUDA, Ahmad SETTİN

Tnf-α-308 and ınf-γ+874 gene polymorphisms in re- lation to susceptibility and severity of type 2 diabe- tes mellitus among egyptian cases

Mısırlı tip 2 diabetus mellitus (DM) olgularında TNF-α-308 ve INF-γ+874 Gen Polimorfizmi ilişkisini araştırmak. Katılımcılar 93 erkek ve 114 kadın tip 2 DMlu olgudan oluştu. Ortalama yaş 57ydi. Benzer çevreden farklı 212 sağlıklı kontrol grubu ile karşılaştırıldı. TNF-α-308 (G/A) ve IFN-γ+874 (A/T) ilişkili polimorfizmin tespiti için sekans spesifik primerli PCR kullanılarak DNA çoğaltıldı. TNF-α-308 (AA) ve IFN-γ+874 (A/A)nın kombine homozigot paterni kontrollerle karşılaştırıldığında diabetiklerde anlamlı yüksekti (p=0.023),bu (anlamlı olmasa da) komplike, kontrolsüz olgular ve belirgin insülin dirençli olgularda belirgindi. TNF-α-308 AA ve IFN-γ 874 AA ile ilgili polimorfizm aile danışmanlığı ve yönetimi üzerindeki potansiyel etkisi ile Mısır bireylerde tip 2 DM için genetik bir belirteç olarak kabul edilebilir.

Mısırlı Olgularda tnf-α-308 ve ınf-γ+874 gen polimorfizmini tip 2 diabetus mellitus şiddeti ve duyarlılık ilişkisi

To explore the association of TNF-α-308 and IFN- γ +874 genetic polymorphisms with type 2 diabetes mellitus (DM) in Egyptian cases. Participants included 207 cases with type 2 DM, 93 males and 114 females. Their mean age was 57 years. They were com- pared to a control group of 212 healthy unrelated subjects from the same locality. DNA was amplified using PCR with sequence specific primers for detection of polymorphism related to TNF-α-308 (G/A) and IFN-γ+874 (A/T). The combined homozygote pat- tern of TNF-α-308 (AA) and IFN-γ+874 (A/A) was significantly higher in diabetic cases versus controls (p=0.023) that was manifest (although non-significant) among complicated, uncontrolled cases and cases with marked insulin resistance. Polymorphism related to TNF-α-308 AA and IFN-γ+874 AA may be considered as a genetic biomarker for type 2 DM in Egyptian subjects with potential impact on family counseling and management.

PDF

___

1. Arababadi MK, Pourfathollah AA, Daneshmandi S, et al. Evaluation of Relation between IL-4 and IFN-γ Polymorphisms and Type 2 Diabetes. Iranian J Basic Med Sci 2009;12(2):100-4.
2. Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 2004;27:813-23.
3.Daneshmandi S, Pourfathollah A, Arababadi MK, Hassanshahi G, Rezaeian M, Asiabanha M. Evaluation of relation between IL-4 and IFN- γ polymorphisms and type 2 diabetes. J Mazand Univ Med Sci 2008;18:35-41.
4.Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995;92:2409-15.
5. Wastowski IJ, Peres NT, Simoes RT, et al. Identification of a novel 120 bp allele at the TNFα microsatellite locus. Tissue Antigens 2006;67(4):31820
6. Hajeer AH, Hutchinson IV. Influence of TNF alpha gene polymorphisms on TNF alpha production and disease. Hum Immunol 2001;62(11):11919.
7.Stalenhoef JE, Alisjahbana B, Nelwan EJ, et al. The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus. Eur J Clin Microbiol Infect Dis 2008;27:97-103
8. Cantor MJ, Nickerson P, Bernstein CN. The role of cyto- kine gene polymorphisms in determining disease suscep- tibility and phenotype in inflammatory bowel disease. Am J Gastroenterol 2005;100:113442.
9. Trinder P. Determination of blood glucose using an oxi- dase peroxidase system with an alternative oxygen accep- tor. Ann Clin Biochem 1969;6:24-7.
10. Frier BM, Ashby JP, Nairn IM, Blairs JD. Plasma insulin, C-peptide and glucagons concentration in patients with insulin dependent diabetes treated with chlorpropamide. Diab Metab 1981;7(1):45-9.
11. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis Model of Assessment of insu- lin resistance and beta-cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 1985;28:412-9.
12. Aldener-Cannava A, Olerup O. HLA-DOB1 Low-resolution tying by PCR amplification with sequence-specific primers (PCR-SSP). Eur Immunogenet 1994;21:447-55.
13. Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. ARMS-PCR methodologies to determine IL-10, TNF-alpha, TNF-beta and TGF-beta1 gene polymorphism. Transpl Immunol 1999;7:127-8.
14. Pravica V, Perrey C, Sievens A, Lee JH, Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-gamma gene; absolute correlation with polymorphic CA microsateline marker of high IFN-gamma gene. Hum Immunol 2000;61:863-6.
15. Steven E. Stern, Ken Williams, Eleuterio Ferrannini, Ralph A. DeFronzo, Clifton Bogardus, and Michael P. Stern. Identification of Individuals With Insulin Resistance Using Routine Clinical Measurements. Diabetes 2005;54:333-9.
16. American Diabetes Association. Standards of Medical Care in Diabetes2011. Diabetes Care 2011;34(suppl.1):S11-61.
17. Sullivan PW, Morrato EH, Ghushchyan V, Wyatt HR, Hill JO. Obesity, inactivity, and the prevalence of diabetes and diabetes-related cardiovascular comorbidities in the US, 2000-2002. Diabetes Care 2005;28(7):1599-603.
18. Shiba T, Higashi N, Nishimura Y. Hyperglycemia due to in- sulin resistance caused by interferon-gamma. Diabet Med 1998;15:435-6.
19. Kubaszek A, Pihlajamäki J, Komarovski V, et al. Finnish Diabetes Prevention Study. Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes 2003;52(7):1872-6.
20. Wilson AG, Sympons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor ne- crosis factor alpha promoter on transcriptional activa- tion. Proc Natl Acad Sci USA 1997; 94(7):3195-9.
21. Hoffstedt J, Eriksson P, Hellstrom L, Rossner S, Ryden M, Arner P. Excessive fat accumulation is associated with the TNF alpha-308 G/A promoter polymorphism in women but not in men. Diabetologia 2000;43:117-20.
22. Herrmann SM, Ricard S, Nicaud V, et al. Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity. Eur J Clin Invest 1998;28:59-66.
23. Lee SC, Pu YB, Thomas GN, et al. Tumor necrosis factor alpha gene G-308A polymorphism in the metabolic syn- drome. Metabolism 2000;49(8):1021-4.
24. Settin A, Ismail A, Abo El-Magd M, El-Baz R, Kazamel A. Gene polymorphisms of TNF-a 308 (G/A), IL-1021082 (G/A), IL-62174 (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus. Autoimmunity 2009;42(1):50-5
25. Furuta M, Yano Y, Ito K, et al. Relationship of the tumor necrosis factor-alpha -308 A/G promoter polymorphism with insulin sensitivity and abdominal fat distribution in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2002;56(2):141-5.
26. Tsiavou A, Hatziagelaki E, Chaidaroglou A, Koniavitou K, Degiannis D, Raptis SA. Correlation between intracellular interferon-gamma (IFN-gamma) production by CD4+ and CD8+ lymphocytes and IFN-gamma gene polymorphism in pa- tients with type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA). Cytokine 2005;31(2):135-41.