A refined study of FCRL genes from a genome-wide association study for Graves' disease.
To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves' disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regres...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3591391?pdf=render |
| _version_ | 1818356084423786496 |
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| author | Shuang-Xia Zhao Wei Liu Ming Zhan Zhi-Yi Song Shao-Ying Yang Li-Qiong Xue Chun-Ming Pan Zhao-Hui Gu Bing-Li Liu Hai-Ning Wang Liming Liang Jun Liang Xiao-Mei Zhang Guo-Yue Yuan Chang-Gui Li Ming-Dao Chen Jia-Lun Chen Guan-Qi Gao Huai-Dong Song China Consortium for the Genetics of Autoimmune Thyroid Disease |
| author_facet | Shuang-Xia Zhao Wei Liu Ming Zhan Zhi-Yi Song Shao-Ying Yang Li-Qiong Xue Chun-Ming Pan Zhao-Hui Gu Bing-Li Liu Hai-Ning Wang Liming Liang Jun Liang Xiao-Mei Zhang Guo-Yue Yuan Chang-Gui Li Ming-Dao Chen Jia-Lun Chen Guan-Qi Gao Huai-Dong Song China Consortium for the Genetics of Autoimmune Thyroid Disease |
| author_sort | Shuang-Xia Zhao |
| collection | DOAJ |
| description | To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves' disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in CD19(+) B cells and CD8(+) T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level (P(combined) = 2.27×10(-12) and 7.11×10(-13), respectively). Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs. |
| first_indexed | 2024-12-13T19:51:35Z |
| format | Article |
| id | doaj.art-4d47f18e24bb4837a4327b688e987d21 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T19:51:35Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4d47f18e24bb4837a4327b688e987d212022-12-21T23:33:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5775810.1371/journal.pone.0057758A refined study of FCRL genes from a genome-wide association study for Graves' disease.Shuang-Xia ZhaoWei LiuMing ZhanZhi-Yi SongShao-Ying YangLi-Qiong XueChun-Ming PanZhao-Hui GuBing-Li LiuHai-Ning WangLiming LiangJun LiangXiao-Mei ZhangGuo-Yue YuanChang-Gui LiMing-Dao ChenJia-Lun ChenGuan-Qi GaoHuai-Dong SongChina Consortium for the Genetics of Autoimmune Thyroid DiseaseTo pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves' disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in CD19(+) B cells and CD8(+) T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level (P(combined) = 2.27×10(-12) and 7.11×10(-13), respectively). Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs.http://europepmc.org/articles/PMC3591391?pdf=render |
| spellingShingle | Shuang-Xia Zhao Wei Liu Ming Zhan Zhi-Yi Song Shao-Ying Yang Li-Qiong Xue Chun-Ming Pan Zhao-Hui Gu Bing-Li Liu Hai-Ning Wang Liming Liang Jun Liang Xiao-Mei Zhang Guo-Yue Yuan Chang-Gui Li Ming-Dao Chen Jia-Lun Chen Guan-Qi Gao Huai-Dong Song China Consortium for the Genetics of Autoimmune Thyroid Disease A refined study of FCRL genes from a genome-wide association study for Graves' disease. PLoS ONE |
| title | A refined study of FCRL genes from a genome-wide association study for Graves' disease. |
| title_full | A refined study of FCRL genes from a genome-wide association study for Graves' disease. |
| title_fullStr | A refined study of FCRL genes from a genome-wide association study for Graves' disease. |
| title_full_unstemmed | A refined study of FCRL genes from a genome-wide association study for Graves' disease. |
| title_short | A refined study of FCRL genes from a genome-wide association study for Graves' disease. |
| title_sort | refined study of fcrl genes from a genome wide association study for graves disease |
| url | http://europepmc.org/articles/PMC3591391?pdf=render |
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