TUMOR NECROSIS FACTOR-ALPHA POLYMORPHISM AND SECRETION IN MYASTHENIA GRAVIS |
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Authors: | Yu-zhou Guan Li-ying Cui Yan-feng Li Jun-bao Zhang |
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Affiliation: | Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing. |
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Abstract: | OBJECTIVE: To analyze the relationship between tumor necrosis factor-alpha (TNFalpha) gene promoter -308 polymorphism and myasthenia gravis (MG) in Chinese and analyze secretion of TNFalpha in peripheral blood mononuclear cells (PBMC) in MG patients. METHODS: A biallelic polymorphism at position -308 in the promoter of TNFalpha gene was screened by PCR amplification and NcoI recognition site. One hundred and twenty-three MG cases and 115 healthy controls were included in this study. MG patients were classified to different groups according to clinical type, age at onset, and sex respectively. PBMC were isolated from 20 patients and 20 healthy controls, and then cultured in the presence or absence of phytohemagglutinin (PHA) and acetycholine receptors (AchR). The supernatants were harvested after incubation and stored until TNFalpha was assayed by enzyme-linked immunosorbent assay. RESULTS: The frequency of TNFalpha-308 allele 2 (A) was found significantly increase in MG patients and showed a trend especially in late onset (> or =40 years) and male patients (P < 0.05). The allele A had no relationship with thymic pathogenesis in MG patients. But frequency of allele A was significantly higher in general type than in ocular type (P < 0.05). MG patients had a higher inducible level of TNFalpha by PHA and AchR, and could be down regulated after treatment. CONCLUSION: Polymorphism in TNFalpha gene promoter -308 is associated with onset of MG. The microsatellite allele TNFalpha2 confer risk for the development of MG in Chinese patients. MG patients have a higher inducible level of TNFalpha. |
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Keywords: | myasthenia gravis tumor necrosis factor allele polymorphism MYASTHENIA GRAVIS SECRETION POLYMORPHISM NECROSIS risk development Chinese patients microsatellite associated treatment inducible level general type ocular pathogenesis male increase trend especially late |
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