Tamaki Shigehiro, Sanefuzi Nobuyuki, Ohgi Kazuhiko, Imai Yuichiro, Kawakami Masayoshi, Yamamoto Kazuhiko, Ishitani Akiko, Hatake Katsuhiko, Kirita Tadaaki
Department of Oral and Maxillofacial Surgery, Nara Medical University, Nara, Japan.
J Oral Pathol Med. 2007 Jul;36(6):351-6. doi: 10.1111/j.1600-0714.2007.00539.x.
Recently, a new polymorphic gene family called the major histocompatibility complex class I chain-related gene A (MICA) was discovered about 40 kb centromeric to HLA-B gene. The MICA protein, expressed on epithelial cells and many kinds of tumor cells, serves to regulate immune function. The MICA protein is thought to activate immune function on mucosal tissue by binding to NKG2D which is expressed on most natural killer cells, CD8 positive T cells, and gamma delta T cells. An association between MICA gene polymorphisms and the development of oral squamous cell carcinoma (OSCC) has also been reported.
This study was designed to test this association in Japanese patients with OSCC.
The (GCT)(n) polymorphisms of the MICA gene was investigated in 123 patients with OSCC and 188 normal controls using polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis.
Five alleles, namely A4, A5, A6, A9, and A5.1, were found in both groups. The phenotype frequency of the MICA-A5.1 allele was significantly higher in patients with OSCC when compared with normal controls (OR 1.707, 95% CI 0.76-3.45, P=0.042). Also, the microsatellite frequency of the MICA-A5.1 allele was significantly higher in patients with OSCC compared with normal controls (OR 1.664, 95% CI 0.82-3.42, P=0.021). Lastly, the frequency of the MICA-A5.1 allele was significantly higher in those with lymph node metastasis from OSCC compared with normal controls (OR 2.605, 95% CI 1.14-5.27, P=0.026).
These results suggest that the MICA-A5.1 allele may be associated with an increased susceptibility to OSCC in Japan.
最近,一个名为主要组织相容性复合体I类链相关基因A(MICA)的新多态性基因家族在距HLA - B基因着丝粒约40 kb处被发现。MICA蛋白在上皮细胞和多种肿瘤细胞上表达,起到调节免疫功能的作用。MICA蛋白被认为通过与大多数自然杀伤细胞、CD8阳性T细胞和γδT细胞上表达的NKG2D结合来激活黏膜组织的免疫功能。也有报道称MICA基因多态性与口腔鳞状细胞癌(OSCC)的发生有关。
本研究旨在检测日本OSCC患者中的这种关联。
采用聚合酶链反应扩增和变性聚丙烯酰胺凝胶电泳技术,对123例OSCC患者和188例正常对照者的MICA基因(GCT)n多态性进行研究。
两组均发现了5个等位基因,即A4、A5、A6、A9和A5.1。与正常对照相比,OSCC患者中MICA - A5.1等位基因的表型频率显著更高(比值比1.707,95%可信区间0.76 - 3.45,P = 0.042)。此外,与正常对照相比,OSCC患者中MICA - A5.1等位基因的微卫星频率也显著更高(比值比1.664,95%可信区间0.82 - 3.42,P = 0.021)。最后,与正常对照相比,OSCC发生淋巴结转移者中MICA - A5.1等位基因的频率显著更高(比值比2.605,95%可信区间1.14 - 5.27,P = 0.026)。
这些结果表明,在日本,MICA - A5.1等位基因可能与OSCC易感性增加有关。