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M.T. Irkec, B. Bozkurt, L. Mesci, B. Bulur, F. Ersoy, O. Sanal, M. Orhan, U. Arslan, I. Tezcan; TNF–alpha and IL–10 Gene Polymorphisms in Turkish Glaucoma Patients . Invest. Ophthalmol. Vis. Sci. 2005;46(13):27.
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Purpose: Polymorphisms in cytokine genes can influence immune responses, inflammation, tissue injury and apoptosis. Cytokines,such as TNF–alpha, might regulate cell death in response to conditions that stress retinal neurons in glaucoma. Our aim was to evaluate the association between TNF alpha–308 and IL–10 gene polymorphisms and glaucoma. Methods:219 glaucoma patients (88 males, 131 females) with a mean age of 64.35+11.06 years and 178 healthy subjects (73 males, 105 females) with a mean age of 61.95+10.61 years were enrolled in the study. There were 141 primary open angle glaucoma, 52 exfoliative glaucoma, 16 pigmentary glaucoma, and 10 normal–tension glaucoma cases in the study group. The glaucoma group was further classified as early (80 patients), moderate ( 64 patients) and severe (65 patients) based on the visual field examination. Single–nucleotide polymorphisms in the genes for TNF alpha (–308) and IL–10 (–1082, –819, –592) were analyzed by using PCR–restriction fragment length polymorphism (PCR–RFLP) method. Allele or genotype frequencies between controls and glaucoma patients were compared by X2 test or Fisher's exact X2 test. Statistical significance was defined as p<0.05. Results: The frequencies of genotypes for TNF alpha –308 among healthy subjects were 167 (93.8%) for GG, 9 (5.1%) for GA and 2 (1.1%) for AA, while in the glaucoma group 141 patients (64.4%) were GG, 74 (33.8%) were GA and 4 (1.8%) were AA. The difference in GA distribution among the groups was statistically significant (p=0.000). A significant correlation was found with A allele, which increases transcription of TNF–alpha and the severity of glaucoma (p=0.011). IL–10 haplotypes (arranged as genotypes) ACC/ACC (61 patients; 28.4%) and ACC/ATA (51 patients; 23.7%), associated with low IL–10 production, were significantly higher in the glaucoma group compared to the healthy subjects (18 patients; 10.7% and 30 patients 17.8%, respectively)(p=0.000). No correlation was found between IL–10 polymorphism and severity of glaucoma (p=0.081). Conclusions: Genetic predisposition leading to an abnormal immune response might play role in glaucoma susceptibility and severity. In the future, neuroprotection might be possible by inhibiting the action of cytokines taking role in apoptosis and inflammation.
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