Different gene loci within the HLA-DR and TNF regions are independently associated with susceptibility and severity in Spanish rheumatoid arthritis patients

被引:68
作者
Hajeer, AH
Dababneh, A
Makki, RF
Thomson, W
Poulton, K
González-Gay, MA
García-Porrúa, C
Mattey, DL
Ollier, WER
机构
[1] Univ Manchester, Sch Med, Sch Epidemiol & Hlth Sci, ARC Epidemiol Unit, Manchester M13 9PT, Lancs, England
[2] BAU, Fac Pharm, Beirut, Lebanon
[3] Hosp Xeral Calde Lugo, Div Rheumatol, Lugo, Spain
[4] Haywood Hosp, Staffordshire Rheumatol Ctr, Stoke On Trent ST6 7AG, Staffs, England
来源
TISSUE ANTIGENS | 2000年 / 55卷 / 04期
关键词
HLA-DRB1; RA; Spanish; TNF microsatellites;
D O I
10.1034/j.1399-0039.2000.550405.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associated with rheumatoid arthritis (RA) in a population from Lugo region of northwestern Spain. WI patients (n = 179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n = 145) were recruited. RA susceptibility in this population was pre dominantly associated with DRB1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04, The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was significantly increased in seropositive patients. The rheumatoid arthiritis shared epitope (SE) was associated with increased risk for seropositive and erosive disease and this appeared to operate in a dose-dependent manner, Logistic regression analyses revealed that the TNF microsatellite markers TNFcl and b3 were associated with RA independently of DRB1*04 and the SE. Carriage of a TNF cl allele provided an increased risk of RA in SE-negative and SE-heterozygous individuals, TNFcl and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated with erosive disease which was independent of DRB1*04 and the SE. Further studies will be needed to establish why (TNFcl) polymorphism seemingly associated with low TNF alpha production, is a risk factor for WI.
引用
收藏
页码:319 / 325
页数:7
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