Höhler T, Schäper T, Schneider P M, Meyer zum Büschenfelde K H, Märker-Hermann E
Johannes Gutenberg Universität Mainz, Germany.
Arthritis Rheum. 1998 Aug;41(8):1489-92. doi: 10.1002/1529-0131(199808)41:8<1489::AID-ART20>3.0.CO;2-5.
To investigate the potential association of tumor necrosis factor alpha (TNFalpha) promoter alleles with ankylosing spondylitis.
DNA from 141 HLA-B27 positive Caucasian patients with ankylosing spondylitis and 46 B27-positive and 99 B27-negative healthy Caucasian controls was investigated by polymerase chain reaction amplification of the TNFalpha promoter region and subsequent dot-blot analysis with allele-specific oligonucleotides.
There was a significant decrease in the promoter alleles TNF-238.2 and TNF-308.2 in the ankylosing spondylitis group (266 wild-type alleles, 16 variant alleles) compared with the B27-positive (75 wildtype promoter alleles, 17 variant alleles; P<0.0004) and the B27-negative (159 wild-type promoter alleles, 39 variant alleles; P< 0.00001) control groups. Positivity for the variant promoter alleles conferred protection and a relative risk of 0.3 to B27-positive individuals.
These data indicate that allelic variations in the TNFalpha promoter influence disease susceptibility in HLA-B27 positive individuals. This protective effect of variant promoter alleles could be related to differences in TNFalpha production or could reflect the association of different B27 haplotypes with ankylosing spondylitis.
研究肿瘤坏死因子α（TNFα）启动子等位基因与强直性脊柱炎之间的潜在关联。
采用聚合酶链反应扩增TNFα启动子区域，随后用等位基因特异性寡核苷酸进行点杂交分析，对141例 HLA - B27阳性的白种人强直性脊柱炎患者以及46例B27阳性和99例B27阴性的白种人健康对照者的DNA进行研究。
与B27阳性（75个野生型启动子等位基因，17个变异等位基因；P < 0.0004）和B27阴性（159个野生型启动子等位基因，39个变异等位基因；P < 0.00001）对照组相比，强直性脊柱炎组中启动子等位基因TNF - 238.2和TNF - 308.2显著减少。变异启动子等位基因呈阳性可为B27阳性个体提供保护，相对风险为0.3。
这些数据表明，TNFα启动子的等位基因变异会影响HLA - B27阳性个体的疾病易感性。变异启动子等位基因的这种保护作用可能与TNFα产生的差异有关，或者可能反映了不同B27单倍型与强直性脊柱炎的关联。
