日本人群中细胞毒性T淋巴细胞相关抗原4（CTLA4）多态性等位基因与炎症性肠病的关联
Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese.
作者信息
Machida Haruhisa, Tsukamoto Kazuhiro, Wen Chun-Yang, Narumi Yukiko, Shikuwa Saburou, Isomoto Hajime, Takeshima Fuminao, Mizuta Yohei, Niikawa Norio, Murata Ikuo, Kohno Shigeru
机构信息
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
出版信息
World J Gastroenterol. 2005 Jul 21;11(27):4188-93. doi: 10.3748/wjg.v11.i27.4188.
AIM
To examine an association between the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC) and Crohn's disease (CD) in the Japanese.
METHODS
We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms (SNPs) in CTLA4, such as C-318T in the promoter region, A+49G in exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT)(n) repeat polymorphism in 3'-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using chi (2) and Fisher exact tests.
RESULTS
The frequency of "A/A" genotype at the G+6230A SNP site was statistically lower in UC patients than in controls (3.7% vs 11.0%, P = 0.047, odds ratio (OR) = 0.311). Moreover, the frequency of "G/G" genotype at the A+49G SNP site was significantly higher in CD patients with fistula (48.6%) than those without it (26.2%) (P = 0.0388, OR=2.67).
CONCLUSION
The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.
目的
研究在T细胞活化下调中起作用的细胞毒性T淋巴细胞抗原4（CTLA4）基因与日本人群中由溃疡性结肠炎（UC）和克罗恩病（CD）组成的炎症性肠病之间的关联。
方法
我们通过聚合酶链反应-限制性片段长度多态性方法，研究了108例UC患者、79例CD患者和200例性别匹配的健康对照者，检测CTLA4基因的三个单核苷酸多态性（SNP），如启动子区域的C-318T、外显子1的A+49G和3'非翻译区（3'-UTR）的G+6230A，并通过变性序列凝胶上的荧光标记片段分析检测3'-UTR中的（AT）（n）重复多态性。使用卡方检验和Fisher精确检验对患者和对照者之间以及患者亚组之间的等位基因和基因型频率及其分布进行统计学比较。
结果
在G+6230A SNP位点，UC患者中“A/A”基因型的频率在统计学上低于对照组（3.7%对11.0%，P = 0.047，优势比（OR）= 0.311）。此外，在有瘘管的CD患者中，A+49G SNP位点的“G/G”基因型频率（48.6%）显著高于无瘘管的患者（26.2%）（P = 0.0388，OR = 2.67）。
结论
结果表明，位于2q33的CTLA4是UC的一个决定因素，并且与日本CD患者的瘘管形成有关。
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