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KMID : 0357119980200040443
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Korean Journal of Immunology
1998 Volume.20 No. 4 p.443 ~ p.449
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Tumor Necrosis Factor Alpha Promoter Polymorphism of Systemic Lupus Erythematosus in Korean
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박경숙/1Kyung-Sook Park
2Sang-Heon Lee/2Jee-Won Mok/2Ho-Youn Kim
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Abstract
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It was reported that polymorphism of TNF alpha gene was present in promoter region and involves the substitution of guanine by adenosine in the uncommon (TNFA 2) allele. In this study, we investigated the significance of TNFA gene polymorphism in relation to various clinical characteristics and autoantibody profiles in SLE as well as comparing it with that of other countries, and also studied its association with peripheral TNF-a production in vitro. TNFA genotyping was performed in 126 SLE patients and 300 controls using DNA extracted from peripheral leucocytes. The biallelic polymorphism at position -308 of the TNFA promotor was determined by Ncol- RFLP. Peripheral mononuclear cell production of TNF-a was investigated by bioassay using L-929 cell cytotoxicity. The TNFA "1 homozygote was a predominant allele (77.0%) in SLE, which was not different from the controls. TNFA "2 homozygate was extremely rare in both patients and controls (0.8%, 1.3% respectively). The clinical manifestations between TNFA '1 and TNFA"2 did not differ. The production of autoantibodies including dsDNA, anti-La, anti-nRNP and anti-Sm was not different between two alleles, whereas anti- Ro antibody was more frequent in TNFA"1/TNFA '1 than in TNFA'1/TNFA'2 (62.1% vs 38.4%, P=0.022). The polymorphism of TNFA gene did not influence the lipopolysaccharide stimulated peripheral mononuclear cell production of TNF-a (1356+-293 vs 1119+-385 pg/ml; TNFA'1/TNFA'1, TNFA'1/TNFA'2 respectively). These results suggested that promoter polymorphism of TNFA was not directly involved in the susceptibility of SLE and was not responsible for differential peripheral TNF-a production, but TNFA ' may be associated with anti-Ro antibody production.
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KEYWORD
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SLE, TNFA gene, Anti-Ro,
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