肿瘤坏死因子 -308A 等位基因和 HLA -DR3 等位基因独立地增加系统性红斑狼疮的易感性。

TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus.

作者信息

Rood M J, van Krugten M V, Zanelli E, van der Linden M W, Keijsers V, Schreuder G M, Verduyn W, Westendorp R G, de Vries R R, Breedveld F C, Verweij C L, Huizinga T W

机构信息

Leiden University Medical Center, The Netherlands.

出版信息

Arthritis Rheum. 2000 Jan;43(1):129-34. doi: 10.1002/1529-0131(200001)43:1<129::AID-ANR16>3.0.CO;2-S.

DOI:10.1002/1529-0131(200001)43:1<129::AID-ANR16>3.0.CO;2-S

PMID:10643708

Abstract

OBJECTIVE

To evaluate the respective contributions of tumor necrosis factor (TNF) promoter polymorphisms and HLA-DR alleles to susceptibility to systemic lupus erythematosus (SLE).

METHODS

TNF-238G/A and 308G/A promoter polymorphisms and HLA-DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to assess the magnitude of the susceptibility factors. The presence or absence of the SLE classification criteria was determined and correlated with the TNF promoter and HLA-DRB1 genotypes.

RESULTS

The frequency of the TNF-308A/A and 308G/A genotypes was significantly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 238A/A genotypes were equally prevalent in SLE patients and controls. The HLA-DR3 specificity (DRBI*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4). Stratification to correct for interdependence of the 2 loci confirmed the association of both TNF-308A and HLA-DR3 with SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlation was found between TNF promoter and HLA-DRB1 genotypes and any SLE classification criterion or disease manifestation.

CONCLUSION

TNF-308A and HLA-DR3 alleles are independent susceptibility factors for SLE.

摘要

目的

评估肿瘤坏死因子（TNF）启动子多态性和HLA - DR等位基因对系统性红斑狼疮（SLE）易感性的各自贡献。

方法

测定了99例连续的白种人SLE患者和177例白种人对照者的TNF - 238G/A和308G/A启动子多态性以及HLA - DRB1等位基因。计算标准比值比和Mantel - Haenszel比值比以评估易感性因素的大小。确定SLE分类标准的存在与否，并将其与TNF启动子和HLA - DRB1基因型相关联。

结果

SLE患者中TNF - 308A/A和308G/A基因型频率显著更高（比值比5.0）。相反，TNF - 238G/A和238A/A基因型在SLE患者和对照者中同样普遍。HLA - DR3特异性（DRBI*0301等位基因）在SLE人群中显著更普遍（比值比4.4）。对两个位点的相互依赖性进行分层校正后，证实TNF - 308A和HLA - DR3均与SLE相关（Mantel - Haenszel比值比分别为3.2和2.4）。未发现TNF启动子和HLA - DRB1基因型与任何SLE分类标准或疾病表现之间存在相关性。