A C/T Polymorphism in the 5' Untranslated Region of the CD40 Gene Is Associated with Later Onset of Graves' Disease in Japanese

Abstract

Abstract. Graves' disease (GD) is an autoimmune disorder with genetic predisposition. CD40, which stimulates lymphocyte proliferation and differentiation, is an important immunomodulator and is expressed in the thyroid follicular cells as well as antigen-presenting cells. A single nucleotide polymorphism (SNP) at position -1 of the Kozak sequence of the CD40 gene has been reported to be associated with the development of GD. The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to GD in Japanese. CD40 gene polymorphisms were studied in Japanese GD patients (n = 324) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 229). A C/T polymorphism at position -1 of the CD40 gene was measured using the polymerase chain reaction restriction fragment length polymorphism. There was no significant difference in allele or genotype frequency of the CD40 SNP between GD and control subjects. There was a significant decrease in the TT genotype frequency in the GD patients, who developed GD after 40 years old, than those under 40 year of age. These data suggest that the SNP of CD40 gene is associated with susceptibility to later onset of GD in Japanese.

A CD40 Kozak sequence polymorphism and susceptibility to antibody-mediated autoimmune conditions: the role of CD40 tissue-specific expression

“…Previously, we 12 and others [15][16][17][18] have shown that a SNP, in the Kozak sequence of the CD40 gene, is associated , showing significant CD20 expression only in lymph node, spleen and thymus. All other tissues did not show significant CD20 expression ruling out blood contamination.…”

“…Subsequent case-control association studies demonstrated an association of the CC genotype with GD. 12 With the exception of a sole report, 14 the association between the CC genotype and GD has now been replicated in several studies, performed in different populations, including Caucasians, 12,15 Koreans 16 and Japanese 17,18 (an additional report purporting a lack of association between the C allele and GD 19 was found, upon re-analysis, to show an association between the CC genotype and GD 20 ). Moreover, a meta-analysis of all studies showed a highly significant association between the CC genotype and GD.…”

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

“…The genetic susceptibility of these diseases is thought to be polygenic. It has been reported that major histocompatibility complex (MHC) gene [3,4], cytotoxic T lymphocyte antigen-4 (CTLA-4) gene [4][5][6], thyrotropin receptor (TSHR) gene [7], PTPN22 gene [8], CD40 gene [9,10], interferon-γ (IFN-γ) gene [11], tumor necrosis factor-α (TNF-α) gene [12,13] and interleukin-13 (IL-13) gene [14] polymorphisms are associated with GD and their interactions may influence disease phenotype and severity [3]. However, their contribution to susceptibility to GO awaits confirmation.…”

Genetic effect of an A/G polymorphism in the HSP70 gene on thermotolerance in chicken

“…SNPs in non-coding regions can regulate the binding activity of transcriptional factors by altering the structure of some transcriptional domain binding sites (Jeng et al, 2008;Shibata et al, 2009;Ucisik-Akkaya et al, 2010). Using statistical analysis, Mukai et al (2005) found that SNP in the 5'-untranslated region of the CD40 gene had some influence on its expression, and Ordovás et al (2008) found the g.763G>C SNP in the 5'-untranslated region of the bovine FASN gene affects its promoter activity. Moreover, Sun et al (2010) found that the rs11868112 SNP locus on the 26-kb gene upstream of the RPTOR gene altered the RAR and POU2F1 transcription factor binding sites, which led to a decrease in gene expression (as determined by RT-PCR and ChIP methods) in response to climatic adaptations.…”