Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups
Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups
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DOI：
10.1093/hmg/6.8.1275
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发表时间：
1997-08-01
影响因子：
3.5
通讯作者：
She, JX
中科院分区：
文献类型：
--
作者：
Marron, MP;Raffel, LJ;She, JX
使用连锁不平衡（关联）分析来评估CTLA4/CD28基因附近的候选区域，使用多民族收集的有一个或多个儿童患有IDDM的家庭。在本研究独有的数据集中（西班牙语、法语、墨西哥裔美国人、中国人和韩国人），传播/不平衡检验（TDT）显示CTLA4基因3'非翻译区（at）(n)微卫星标记的等位基因传播存在高度显著的偏差（P = 0.002）和第一外显子的a /G多态性（P = 0.00002）。CTLA4 A/G等位基因传播偏差的总体证据在本研究和先前关于美国、意大利、英国、西班牙和撒丁岛家族的报告的综合数据集（669个多重家族和357个单一家族）中也非常显著（P = 0.00005）。在这些数据集中观察到显著的异质性。英国、撒丁岛和中国的数据集没有显示出A/G多态性的任何偏差，而高加索裔美国人的数据集显示出微弱的传输偏差。在三个地中海-欧洲人群（意大利、西班牙和法国）（P = 10(-5)）、墨西哥裔美国人群（P = 0.002）和韩国人群（P = 0.03）中发现了强烈的传播偏差。这些结果表明，一个真正的IDDM易感位点（IDDM12）位于CTLA4附近。
Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)(n) microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.