Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population

Mutations in CD40 have been widely reported to be risk factors for Graves’ disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorp...

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Autores principales:	He Jiang, Fei-Fei Yuan, Hai-Ning Wang, Wei Liu, Xiao-Ping Ye, Shao-Ying Yang, Hui-Jun Xie, Sha-Sha Yu, Yu-Ru Ma, Le-Le Zhang, Shuang-Xia Zhao, Huai-Dong Song, The China Consortium for the Genetics of Autoimmune Thyroid Disease
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Graves’ disease single nucleotide polymorphisms CD40 association analysis expression quantitative trait locus Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/cf205bfd803540a3a5e7d83459702134
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spelling	oai:doaj.org-article:cf205bfd803540a3a5e7d834597021342021-11-18T12:52:30ZCompelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population1664-239210.3389/fendo.2021.759597https://doaj.org/article/cf205bfd803540a3a5e7d834597021342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.759597/fullhttps://doaj.org/toc/1664-2392Mutations in CD40 have been widely reported to be risk factors for Graves’ disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorphism (SNP) of CD40, and has been confirmed to predispose those with the alteration to GD, regardless of ethnicity. Our genome-wide association study (GWAS) indicated that several SNPs, including rs1883832 located within the vicinity of CD40 were associated with GD in the Han Chinese population. Aiming at identifying the most consequential SNP and its underlying pathogenic mechanism, we performed a two-stage refined study on 8,171 patients with GD and 7,906 controls, and found rs1883832 was the most significantly GD-associated SNP in the CD40 gene region (PCombined = 9.17×10-11, OR = 1.18). Through searching the cis-expression quantitative trait locus database and using quantitative RT-PCR, we further discovered that the rs1883832 genotype can influence CD40 gene transcription. Furthermore, we demonstrated that rs1883832 is a susceptibility locus for pTRAb+ GD patients. In conclusion, the current study provides robust evidence that rs1883832 can regulate CD40 gene expression and affect serum TRAb levels, which ultimately contributes to the development of GD.He JiangFei-Fei YuanHai-Ning WangWei LiuWei LiuXiao-Ping YeShao-Ying YangHui-Jun XieSha-Sha YuYu-Ru MaLe-Le ZhangShuang-Xia ZhaoHuai-Dong SongThe China Consortium for the Genetics of Autoimmune Thyroid DiseaseFrontiers Media S.A.articleGraves’ diseasesingle nucleotide polymorphismsCD40association analysisexpression quantitative trait locusDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Graves’ disease single nucleotide polymorphisms CD40 association analysis expression quantitative trait locus Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Graves’ disease single nucleotide polymorphisms CD40 association analysis expression quantitative trait locus Diseases of the endocrine glands. Clinical endocrinology RC648-665 He Jiang Fei-Fei Yuan Hai-Ning Wang Wei Liu Wei Liu Xiao-Ping Ye Shao-Ying Yang Hui-Jun Xie Sha-Sha Yu Yu-Ru Ma Le-Le Zhang Shuang-Xia Zhao Huai-Dong Song The China Consortium for the Genetics of Autoimmune Thyroid Disease Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population
description	Mutations in CD40 have been widely reported to be risk factors for Graves’ disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorphism (SNP) of CD40, and has been confirmed to predispose those with the alteration to GD, regardless of ethnicity. Our genome-wide association study (GWAS) indicated that several SNPs, including rs1883832 located within the vicinity of CD40 were associated with GD in the Han Chinese population. Aiming at identifying the most consequential SNP and its underlying pathogenic mechanism, we performed a two-stage refined study on 8,171 patients with GD and 7,906 controls, and found rs1883832 was the most significantly GD-associated SNP in the CD40 gene region (PCombined = 9.17×10-11, OR = 1.18). Through searching the cis-expression quantitative trait locus database and using quantitative RT-PCR, we further discovered that the rs1883832 genotype can influence CD40 gene transcription. Furthermore, we demonstrated that rs1883832 is a susceptibility locus for pTRAb+ GD patients. In conclusion, the current study provides robust evidence that rs1883832 can regulate CD40 gene expression and affect serum TRAb levels, which ultimately contributes to the development of GD.
format	article
author	He Jiang Fei-Fei Yuan Hai-Ning Wang Wei Liu Wei Liu Xiao-Ping Ye Shao-Ying Yang Hui-Jun Xie Sha-Sha Yu Yu-Ru Ma Le-Le Zhang Shuang-Xia Zhao Huai-Dong Song The China Consortium for the Genetics of Autoimmune Thyroid Disease
author_facet	He Jiang Fei-Fei Yuan Hai-Ning Wang Wei Liu Wei Liu Xiao-Ping Ye Shao-Ying Yang Hui-Jun Xie Sha-Sha Yu Yu-Ru Ma Le-Le Zhang Shuang-Xia Zhao Huai-Dong Song The China Consortium for the Genetics of Autoimmune Thyroid Disease
author_sort	He Jiang
title	Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population
title_short	Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population
title_full	Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population
title_fullStr	Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population
title_full_unstemmed	Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population
title_sort	compelling evidence linking cd40 gene with graves’ disease in the chinese han population
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cf205bfd803540a3a5e7d83459702134
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Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population

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