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

Mutations in 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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Published in:Frontiers in endocrinology (Lausanne) 2021-11, Vol.12, p.759597-759597
Main Authors: Jiang, He, Yuan, Fei-Fei, Wang, Hai-Ning, Liu, Wei, Ye, Xiao-Ping, Yang, Shao-Ying, Xie, Hui-Jun, Yu, Sha-Sha, Ma, Yu-Ru, Zhang, Le-Le, Zhao, Shuang-Xia, Song, Huai-Dong
Format: Article
Language:English
Subjects:
Asians - genetics
association analysis
CD40
CD40 Antigens - genetics
Chromosomes, Human, Pair 20
Cohort Studies
Endocrinology
expression quantitative trait locus
Female
Graves Disease - genetics
Graves’ disease
Humans
Male
Polymorphism, Single Nucleotide
single nucleotide polymorphisms
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Summary:Mutations in 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 , 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 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 gene region ( = 9.17×10 , 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 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.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2021.759597