Tristetraprolin (TTP) gene polymorphisms in patients with rheumatoid arthritis and healthy individuals
Tristetraprolin (TTP) gene polymorphisms in patients with rheumatoid arthritis and healthy individuals
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DOI：
10.1007/s10165-008-0085-5
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发表时间：
2008-10-01
影响因子：
2.2
通讯作者：
Sumida, Takayuki
中科院分区：
文献类型：
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作者：
Suzuki, Takeshi;Tsutsumi, Akito;Sumida, Takayuki
Tristetraprolin (TTP) 是一种细胞内蛋白质，通过与细胞因子的 mRNA 结合并使其不稳定来调节细胞因子（包括 TNF α）的产生。因此，TTP基因表达的差异可能会影响炎症性疾病的严重程度，例如类风湿性关节炎（RA）。我们寻找人类 TTP 基因的多态性，为此，我们对 20 个日本个体（10 个患有 RA 和 10 个健康志愿者）的整个 TTP 基因进行了测序，并在启动子区域发现了一个单核苷酸多态性 (SNP)。我们通过限制性片段长度多态性方法在 155 名 RA 患者和 100 名对照受试者中分析了该 SNP (A/G)。虽然该 SNP 中 A 等位基因的频率在 RA 患者 (74.5%) 和对照 (76.0%) 中相似，但基因型 GG 的 RA 患者的病程短于基因型 AA/AG 的患者，且基因型 GG 的 RA 患者接受英夫利昔单抗治疗的可能性更高。我们通过荧光素酶测定研究了两个等位基因之间启动子活性的差异，发现等位基因A的TTP启动子区域的启动子活性比等位基因G的TTP启动子区域高约两倍。我们得出结论，TTP基因启动子区域的该SNP轻微影响启动子活性，因此可能影响包括RA在内的炎症性疾病的疾病活性。
Tristetraprolin (TTP) is an intracellular protein that modulates the production of cytokines, including TNF alpha, by binding to and destabilizing the mRNAs of these cytokines. Therefore, differences in TTP gene expression may affect the severity of inflammatory diseases, such as rheumatoid arthritis (RA). We searched for polymorphisms in the human TTP gene and for this purpose, we sequenced the entire TTP gene in 20 Japanese individuals (ten with RA and ten healthy volunteers) and found one single nucleotide polymorphism (SNP) in the promoter region. We analyzed this SNP (A/G) by restriction fragment length polymorphism method in 155 RA patients and 100 control subjects. While the frequency of A allele in this SNP was similar in RA patients (74.5%) and controls (76.0%), the disease duration in RA patients with genotype GG was shorter than that of patients with genotypes AA/AG and RA patients with genotype GG had a higher probability of being treated with infliximab. We studied the difference in promoter activity between the two alleles by luciferase assay and found that the promoter activity of TTP promoter region with allele A was around two-fold higher than that with allele G. We conclude that this SNP in the promoter region of the TTP gene mildly affects promoter activity, and thus, may influence the disease activity of inflammatory disorders including RA.