甲状腺相关眼病与肿瘤坏死因子α基因启动子区-863C/A多态性相关性的初步研究

目的探讨肿瘤坏死因子仅（TNF-α）基因启动子区-863C／A多态性与甲状腺相关眼病（TAO）的相关性。方法选择2002年7月至2003年12月于我院内分泌门诊就诊的符合本研究人选标准的患者和正常对照者,并抽取外周抗凝血提取基因组DNA,采用多聚酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测76例正常对照者（对照组）、54例TAO患者（TAO组）和60例自身免疫性甲状腺疾病（AITD）无眼病患者（无眼病组）TNF-α基因-863C／A多态性。分析比较此多态位点的基因型和等位基因频率在不同人群中分布的差异。结果（1）TAO组、无眼病组及对照组CA＋AA基因型频率分别为46．3％、30．0％、25．0％,A等位基因频率分别为27．8％、15．0％、12．5％。（2）TAO组A等位基因频率显著高于无眼病组和对照组（P=0．018,P=0．002）。（3）按性别分层后,TAO组男性患者CA＋AA基因型与A等位基因频率均显著高于对照组男性（OR=4．31,P=0．019：OR=4．81,P=0．003）和无眼病组男性患者（OR=4．87,P：0．027;OR=5．38,P=0．008）;而女性患者组间比较差异无统计学意义（均P〉0．05）。（4）TAO组ATA分级5＋6级眼病患者CA＋AA基因型和A等位基因的频率均显著高于无眼病组（OR=20．68,P=0．021;OR=39．67,P〈0．001）。结论TNF-α基因启动子区-863位点A等位基因可能是TAO尤其是男性TAO患者的易感基因。（中华眼科杂志,2005,41：786—790）

The relevance of tumor necrosis factor-alpha gene-863C/A polymorphism with thyroid-associated ophthalmopathy

OBJECTIVE: To investigate the relevance of tumor necrosis factor-alpha (TNF-alpha) gene -863C/A polymorphism with thyroid-associated ophthalmopathy (TAO). METHODS: TNF-alpha gene polymorphism at position -863 was determined by PCR-RFLP in 76 normal people, 54 patients with TAO and 60 patients with autoimmune thyroid disease (AITD) who had no ophthalmopathy. All the subjects were collected from July 2002 to December 2003 in out-patient department of endocrinology in the hospital. The difference of genotype and the variation of allele frequencies were analyzed by Chi-square test. RESULTS: (1) Frequencies distribution of CA + AA genotype in TAO, non-ophthalmopathy and control groups were 46.3%, 30.0%, 25.0% respectively, and allele A were 27.8%, 15.0%, 12.5% for those three groups respectively. (2) Frequencies of allele A in TAO group were significantly higher than those in non-ophthalmopathy and control groups (P = 0.018 and 0.002 respectively). (3) When the three groups were stratified according to sex, frequencies of -863 CA + AA genotype and allele A in male TAO patients were significantly higher than those in control group (OR = 4.31, P = 0.019; OR = 4.81, P = 0.003) and non-ophthalmopathy group (OR = 4.87, P = 0.027; OR = 5.38, P = 0.008). No significant difference was found in female patients (P > 0.05). (4) Frequencies of CA + AA genotype and allele A in TAO patients with 5 + 6 grade were significantly higher than those in non-ophthalmopathy group (CA + AA genotype: OR = 20.68, P = 0.021; allele A: OR = 39.67, P < 0.001). CONCLUSION: Allele A of TNF-alpha gene at position -863 may be associated with TAO especially in male patients.