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

Abstract

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.

A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population

“…Additionally, it impedes HBV DNA replication and facilitates immune recovery subsequent to HBV infection. It is noteworthy that the aforementioned findings primarily pertain to B cells within PBMCs, as opposed to monocytes, thereby aligning with the findings of Jiang et al 26 In their study, Jiang and colleagues demonstrated a marked elevation of CD40 expression in CD19 + B cells compared to CD14 + monocytes. Furthermore, they noted that the CC/CT genotype of rs1883832 exhibited heightened CD40 expression specifically in CD19 + B cells, while such an association was not observed in CD14 + monocytes.…”

“…Recent research has identified single-nucleotide polymorphisms (SNPs) in CD40’s Kozak sequence that may affect the start of transcription, and studies have also suggested that SNPs in CD40 are closely linked to autoimmune diseases. 7 , 10 , 11 SNPs in CD40 have the potential to alter CD40’s function, thereby affecting protein expression or activity, and may play a potential role in HBV infection.…”