台灣本土僵直性脊椎炎腫瘤壞死因子啟動子區域基因多型性之分析

Analysis of Tumor Necrosis Factor-a Promoter G-238A and G-308A Polymorphisms in Taiwanese Patients with Ankylosing Spondylitis

駱梅桂(Mei-kuei Lo)

指導教授 ： 張懿欣教授

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2005年)

摘要

影響僵直性脊椎炎(ankylosing spondylitis)的基因因子當中，HLA-B27只佔了20%至50%的因素，流行病學研究認為組織相容性複合物基因群尚有其他基因，在僵直性脊椎炎致病機轉過程中扮演重要角色。甲型腫瘤壞死因子(tumor necrosis factor；TNF-α)屬於促發炎細胞激素(proinflammatory cytokine)，對於關節破壞的免疫調控作用具有影響力，其基因位於人類第六號染色體之短臂(6p21.3)，而且已知有許多單核苷酸多型性(single nucleotide polymorphisms；SNPs)會影響TNF-α基因的功能。然而這些單核苷酸多型性的對偶基因本身以及它們和自體免疫疾病之間的關係仍然不是非常清楚。本篇研究的目的是想探討TNF-α啟動子G-238A和G-308A的基因多型性與台灣本土僵直性脊椎炎患者之間的關係。本研究共收集143位僵直性脊椎炎患者和112位非僵直性脊椎炎健康個體血液檢體，抽取血球細胞之基因DNA並利用聚合酶連鎖反應 (polymerase chain reaction；PCR)和限制片段長度多型性(restriction fragment length polymorphism；RFLP)之方法，偵測TNF-α啟動子G-238A和G-308A的基因多型性。結果發現僵直性脊椎炎患者的TNF-α啟動子-238G與-308G對偶基因型性有意義的增加，顯示TNF-α啟動子G-238A和G-308A的基因多型性分佈與台灣僵直性脊椎炎有明顯統計學上的關聯性。

關鍵字

僵直性脊椎炎

並列摘要

Genetic factors appear to account for the majority of the susceptibility to ankylosing spondylitis (AS), although HLA-B27 probably accounts for only 20-50% of the attributable disease risk. Several epidemiologic studies have suggested that there are other genes within the major histocompatibility complex (MHC) contribute to disease risk. Tumor necrosis factor-α(TNF-α) is a potent proinflammatory cytokine and immune modulator of joint destruction. The TNF-αgene has been mapped to chromosome 6p21.3 and many single nucleotide polymorphisms (SNPs) that could affect its function have been detected within the gene. The allele frequencies of these SNPs and their relationship to autoimmune disease remain largely unknown. The aims of this study were to examine the putative relationship between the incidence of AS in Taiwanese and two polymorphisms of the TNF-α promoter region (position -238 and -308). Peripheral blood sample were collected and genomic DNA was extracted from 143 patients with AS and 112 healthy controls study subjects. TNF-α G-238A and G-308A polymorphisms were analyzed by PCR and RFLP analysis. There was a significant increase in the promoter alleles TNF-α -238G and -308G in the AS. Our results revealed that TNF-α G-238A and G-308A polymorphisms were associated with AS.

並列關鍵字

AS ； ankylosing spondylitis

參考文獻

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