肿瘤坏死因子-α基因启动子区域-308多态与国人骨关节炎易感性的相关性分析

Association of tumor necrosis factor-alpha-308 polymorphism with osteoarthritis in a Chinese population

目的探讨肿瘤坏死因子—α基因启动子区域-308（TNF-α-308）多态与骨关节炎（OA）遗传易感性的关系。方法随机选取2011年3月至2012年7月收治的200例膝关节OA患者（OA组）和同地区、无血缘关系的305名健康人群（对照组），均为汉族。采用TaqMan方法榆测其TNF—α-308坫因型分布及差异。OA组患者具有明确的OA症状、体征和影像学证据。两组研究对象的性别、年龄差异均无统计学意义（P〉0．05），具有可比性。结果OA组和对照组的TNF-α-308A等位基因频率分别为16．0％和8．7％，A等位基因的OA发病风险是G等位基因的2．00倍[95％CI（1.35，2．94），P=0．000]。GA杂合子、AA纯合子和A等位基因携带者（GA或AA基因型）的OA风险分别是GG纯合子的2．03倍[95％CI（1．27，3．27），P=0．003]、5．29倍[95％CI（1．00，27．99，P=0．050）]和2．13倍[95％CI（1．35．3．35），P=0．001]。将GG、GA和AA视为不同的等级，存在等位基因剂量-效应关系（P〈0．05）。结论TNF-α-308A可增加OA发病风险，该多态可作为中国OA高危人群的筛选指标。

Objective To investigate a possible association between TNF-α-308 polymorphism and susceptibility to osteoarthritis （OA） in a Chinese population. Methods We randomly recruited 200 OA patients who sought medical treatment in our department from March 2011 to July 2012 and 305 heahhy controis in tile same area. Their TNF-α-308 genotypes were determined by TaqMan assay and compared. All the subjects belonged to the Han ethnic group. The OA group had definite symptoms, signs and radiological evidence of the disease. The 2 groups were compatible in gender and age （ P 〉 0. 05） . Results The frequency of -308A allele was 0. 160 in the OA group and 0. 087 in the controls. Thus the -308A allele had a risk for OA 2. 00-fold [95% CI （ 1.35, 2.94）, P =0. 000] higher than the -308G allele. When compared to GG homozygote, GA heterozygote had a risk for OA 2.03-fold higher [95% CI （1.27, 3.27）, P = 0. 003], AA homozygote had a risk 5.29-fold higher [95% CI （1.00, 27.99）, P = 0. 050] and carriers of the -308A allele （GA or AA genotypes） had a risk 2. 13-iohl higher [95% CI （l. 35, 3.35）, P =0. 001 ]. Taking GG, GA and AA as different grades, the Armitage＇s trend test showed a dose-effect relationship in the alleles. Conclusion Since the TNF-c＋-3OSA contributes to the elevated OA risk, this polymorphism can be used as a screening marker to identify individuals at risk for OA in the Chinese population.