Evaluation of microsatellite markers in association studies: a search for an immune-related susceptibility gene in sarcoidosis
Evaluation of microsatellite markers in association studies: a search for an immune-related susceptibility gene in sarcoidosis
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DOI：
10.1007/s00251-004-0753-3
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发表时间：
2005-03-01
期刊：
影响因子：
3.2
通讯作者：
Keicho, N
中科院分区：
文献类型：
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作者：
Tanaka, G;Matsushita, I;Keicho, N
已提出利用候选基因座与邻近标记之间的连锁不平衡(LD)进行关联研究，以确定复杂疾病的易感基因。我们分析了与Th1免疫反应相关的候选基因被注释的区域的微卫星(MSS)和LD模式的多态，并试图在基于标记的关联研究中确定结节病的易感基因。在6个Th1相关基因(IFNGR1、IFNGR2、IL12RBI、IL12RB2、STAT1和STAT4)中鉴定出19个MS，其中8个被进一步鉴定为有用的多态标记。在这些候选基因的5‘端和3’端均存在单核苷酸多态(SNPs)，其中至少有一个MS标记等位基因与这些SNPs之间的r(2)值大于0.1。STAT4附近的一个MS等位基因与结节病显著相关，LD中带有MS标记的一簇SNPs与结节病相关。这些结果表明，不仅利用SNPs，还利用候选基因内或附近的多等位基因MS进行关联研究，将是寻找疾病易感基因的有用标记，特别是在LD结构未知的人群中。
Association studies using linkage disequilibrium (LD) between candidate loci and nearby markers have been proposed to identify susceptibility genes for complex diseases. We analyzed polymorphisms of microsatellites (MSs) and LD patterns of the regions in which candidate genes related to the Th1 immune response have been annotated and attempted to identify a susceptibility gene for sarcoidosis in a marker-based association study. Nineteen MSs were identified in six Th1-related genes (IFNGR1, IFNGR2, IL12RBI, IL12RB2, STAT1 and STAT4) and then eight were further characterized as useful polymorphic markers. Most of these MSs showed LD with single nucleotide polymorphisms (SNPs) on both 5' and 3' ends of these candidate genes, in which r(2) values between at least one of the MS marker alleles and the SNPs were higher than 0.1. A significant association with one MS allele near STAT4 was shown and a cluster of SNPs in LD with the MS marker was associated with sarcoidosis. These results suggest that association studies using not only SNPs but also multi-allelic MS within or near candidate loci would be useful markers to search for a disease susceptibility gene, especially in populations with unknown LD structure.