Genetic heterogeneity of susceptibility gene in different ethnic populations: refining association study of PTPN22 for Graves' disease in a Chinese Han population.
Genetic heterogeneity of susceptibility gene in different ethnic populations: refining association study of PTPN22 for Graves' disease in a Chinese Han population.
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不同民族人群易感基因遗传异质性：PTPN22与中国汉族格雷夫斯病的关联细化研究
DOI：
10.1371/journal.pone.0084514
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Song H
中科院分区：
文献类型：
--
作者：
Xue L;Pan C;Gu Z;Zhao S;Han B;Liu W;Yang S;Yu S;Sun Y;Liang J;Gao G;Zhang X;Yuan G;Li C;Du W;Chen G;Chen J;Song H
在我们以前的研究中，我们推测Graves病(GD)的亚型可能是由不同的主要易感基因或单个易感基因的不同变异引起的。然而，需要更多的证据来支持这一假设。PTPN22的单核苷酸多态(SNP)rs2476601是欧洲人群中GD的易感基因。然而，这种多态并未在亚洲人群中发现。本研究旨在探讨PTPN22是否为中国人群中GD的易感基因，并进一步确定PTPN22在GD中的易感变异。我们对1,536名GD患者和1,516名对照受试者进行了基于我们的全基因组关联研究(GWAS)结果的归因分析。推测表明，含有PTPN22的连锁不平衡(LD)区块上的255个常见SNP与GD相关(P<；0.05)。在包括4,368名GD患者和4,350名匹配对照的大队列中，选择了9个捕捉到255个常见变异的标签SNPs进行进一步的基因分型。在重复研究中，9个标签SNPs(P>；0.05)在患者和对照组之间的基因分布或等位基因频率上没有显著差异。尽管联合分析显示出弱关联信号(rs3811021的P合并=0.003263)，但假阳性报告概率分析表明它最有可能是假阳性发现。我们的研究不支持中国汉族人群中PTPN22 LD区常见SNP与GD的关联。提示不同民族人群的GD可能由不同的易感基因所致。
In our previous studies, we presumed subtypes of Graves’ disease (GD) may be caused by different major susceptibility genes or different variants of a single susceptibility gene. However, more evidence is needed to support this hypothesis. Single-nucleotide polymorphism (SNP) rs2476601 in PTPN22 is the susceptibility loci of GD in the European population. However, this polymorphism has not been found in Asian populations. Here, we investigate whether PTPN22 is the susceptibility gene for GD in Chinese population and further determine the susceptibility variant of PTPN22 in GD. We conducted an imputation analysis based on the results of our genome-wide association study (GWAS) in 1,536 GD patients and 1,516 control subjects. Imputation revealed that 255 common SNPs on a linkage disequilibrium (LD) block containing PTPN22 were associated with GD (P<0.05). Nine tagSNPs that captured the 255 common variants were selected to be further genotyped in a large cohort including 4,368 GD patients and 4,350 matched controls. There was no significant difference between the nine tagSNPs (P>0.05) in either the genotype distribution or allelic frequencies between patients and controls in the replication study. Although the combined analysis exhibited a weak association signal (P combined = 0.003263 for rs3811021), the false positive report probability (FPRP) analysis indicated it was most likely a false positive finding. Our study did not support an association of common SNPs in PTPN22 LD block with GD in Chinese Han population. This suggests that GD in different ethnic population is probably caused by distinct susceptibility genes.
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