Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.
Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.
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发表时间：
1996-09
影响因子：
9.8
通讯作者：
B. Mulcahy;F. Waldron-Lynch;M. McDermott;C. Adams;C. Amos;D. Zhu;R. Ward;D. Clegg;F. Shanahan;M. Molloy;F. O'Gara
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作者：
B. Mulcahy;F. Waldron-Lynch;M. McDermott;C. Adams;C. Amos;D. Zhu;R. Ward;D. Clegg;F. Shanahan;M. Molloy;F. O'Gara
研究了类风湿关节炎（RA）的主要组织相容性复合物III类肿瘤坏死因子-光敏素（TNF-LT）区域（6p21.3）。在50个多重家系中测定了5个TNF微卫星标记的遗传。总共观察到47种不同的单倍型。其中之一，TNF α 6，b5，c1，d3，e3（H1）单倍型，存在于35.3%的受影响的个体中，但仅在20.5%的未受影响的个体中（P <0.005）。这种单倍型占21.5%的父母单倍型传递到受影响的后代，只有7.3%没有传递到受影响的后代（P = 0.0003）。TNF α 6和TNF c1等位基因与RA个体相关（分别为P = 0.0005和0.0008），HLA-DRB 1“共享表位”（SE）（P = 0.0001）和HLA-DRB 1 *0401（P = 0.0018）也是如此。单因素和双因素条件Logistic回归分析均显示TNF c1和SE在增加RA风险方面具有显著作用（P <0.001）。根据SE的存在进行分层，表明SE杂合子中TNF c1等位基因（P = .0003）和HLA A1、B8、DR 3扩展单倍型（总是TNF a2、b3、c1、d1、e3）（P = .0027）的独立效应，而SE纯合子中H1单倍型与RA相关（P = .0018）。TNF-LT区域似乎影响RA的易感性，与HLA-DR不同。
The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF c1 alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 "shared epitope" (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF c1 and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.