Roschmann E, Wienker T F, Volk B A
Department of Internal Medicine, Division of Gastroenterology, University of Freiburg, Germany.
J Mol Med (Berl). 1996 Feb;74(2):93-8. doi: 10.1007/BF00196784.
There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha10501, beta10201) heterodimer encoded by the alleles HLA-DQA10501 and HLA-DQB10201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.
乳糜泻易感性受强大的遗传影响。虽然在绝大多数乳糜泻患者中，由等位基因HLA - DQA10501和HLA - DQB10201编码的HLA - DQ(α10501,β10201)异二聚体似乎赋予了主要的疾病易感性，但不能排除其他基因也对疾病易感性有影响，如同卵双胞胎和HLA相同的同胞之间的一致率差异所示（分别为70%和30%）。显然，参与T细胞介导免疫反应遗传控制的其他基因可能会影响乳糜泻的易感性。在乳糜泻患者的空肠上皮中，使用γδT细胞受体（TCR）的T细胞密度显著增加，这种异常被认为是乳糜泻所特有的。这表明γδT细胞参与了该疾病的发病机制。为了确定TCRδ（TCRD）基因是否有助于乳糜泻易感性，我们使用位于14q11.2染色体上TCRD位点的高度多态性微卫星标记进行了关联研究和遗传连锁分析。关联研究表明，乳糜泻患者和对照组之间TCRD基因标记的等位基因频率没有显著差异；因此，相对风险估计未达到统计学显著水平。在对23个家庭进行的连锁分析中，针对乳糜泻与TCRD基因标记计算的优势对数（LOD）分数排除了连锁关系，表明在所分析的TCRD基因标记处或其5 cM范围内没有决定因素对乳糜泻状态有影响。总之，本研究结果没有提供证据表明所分析的TCRD基因对乳糜泻易感性有实质性贡献。
