Association of CD40 Gene Polymorphism (C-1T) with Susceptibility and Phenotype of Graves' Disease

Kuryłowicz, Alina; Kula, Dorota; Płoski, Rafał; Skórka, Agata; Jurecka‐Lubieniecka, Beata; Zebracka, Jadwiga; Steinhof-Radwańska, Katarzyna; Hasse-Lazar, Kornelia; Hiromatsu, Yuji; Jarząb, Barbara; Bednarczuk, Tomasz

doi:10.1089/thy.2005.15.1119

Cited by 60 publications

(55 citation statements)

References 38 publications

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“…Our results are also in agreement with Kurylowicz et al 14 who analysed functional polymorphism in the CD40 gene at position -1 in 556 patients with GD and 611 healthy subjects in a Polish population. They reported that although the frequency of C/C genotype was increased in GD compared to controls, the difference was not statistically significant.…”

Section: Discussionsupporting

confidence: 93%

Association of single nucleotide polymorphism in CD28(C/T-I3 + 17) and CD40 (C/T-1) genes with the Graves disease

Mustafa¹,

Fatima

Fatima³

et al. 2018

J Pak Med Assoc

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Objective: To find out a correlation between the single nucleotide polymorphisms in cluster of differentiation 28 and cluster of differentiation 40 genes with Graves' disease, if any. Methods: This case-control study was conducted at the Multan Institute of Nuclear Medicine and Radiotherapy, Multan, Pakistan, and comprised blood samples of Graves' disease patients and controls. Various risk factors were also correlated either with the genotype at each single-nucleotide polymorphism or with various combinations of genotypes studied during present investigation. Results: Of the 160 samples, there were 80(50%) each from patients and controls. Risk factor analysis revealed that gender (p=0.008), marital status (p<0.001), education (p<0.001), smoking (p<0.001), tri-iodothyronine (P <0.001), thyroxin (p<0.001) and thyroid-stimulating hormone (p<0.000) levels in blood were associated with Graves' disease. Conclusion: Both single-nucleotide polymorphisms in both genes were not associated with Graves' disease, either individually or in any combined form.

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Section: Discussionsupporting

confidence: 93%

Association of single nucleotide polymorphism in CD28(C/T-I3 + 17) and CD40 (C/T-1) genes with the Graves disease

Mustafa¹,

Fatima

Fatima³

et al. 2018

J Pak Med Assoc

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“…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.…”

Section: Discussionmentioning

confidence: 78%

“…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.…”

Section: Introductionmentioning

confidence: 97%

“…Moreover, a meta-analysis of all studies showed a highly significant association between the CC genotype and GD. 15 Recent studies by our laboratory have shed light on possible mechanisms by which the C allele of the CD40 Kozak single nucleotide polymorphism (SNP) can contribute to the etiology of GD. Using in vitro studies, we have demonstrated that the C allele of the CD40 Kozak SNP increases the translational efficiency of nascent CD40 mRNA transcripts, resulting in 15-32% more CD40 protein than that seen in the context of the T allele.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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Previously, we and others have demonstrated the association of a C/T single nucleotide polymorphism (SNP), in the Kozak sequence of CD40, with Graves' disease (GD). Here, using an expanded data set of patients, we confirm the association of the CD40 SNP with GD (n ¼ 210, P ¼ 0.002, odds ratio (OR) ¼ 1.8). Subset analysis of patients with persistently elevated thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibodies (Abs), (TPO/Tg Abs), after treatment (n ¼ 126), revealed a significantly stronger association of the SNP with disease (P ¼ 5.2 Â 10 À5 , OR ¼ 2.5) than in GD patients who were thyroid antibodynegative. However, the CD40 SNP was not associated with TPO/Tg Abs in healthy individuals. Next, we tested the CD40 SNP for association with Myasthenia Gravis (MG), which, like GD is an antibody-mediated autoimmune condition. Analysis of 81 MG patients found no association of the SNP with disease. Functional studies revealed significant expression of CD40 mRNA and protein in the thyroid (target tissue in GD) but not in skeletal muscle (target tissue in MG). Combined, our genetic and tissue expression data suggest that the CD40 Kozak SNP is specific for thyroid antibody production involved in the etiology of GD. Increased thyroidal expression of CD40 driven by the SNP may contribute to this disease specificity.

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“…35,36 Although these results could not be replicated clearly in three subsequent large case-control studies in the United Kingdom and Poland, [37][38][39] metaanalysis suggested that the C/C genotype is associated with sporadic GD. 39,40 No association of disease susceptibility or disease course in MS and MG was found with the CD40À1C4T polymorphism. However, functional studies revealed significant expression of CD40 mRNA and protein in the thyroid (target tissue in GD) but not in skeletal muscle (target tissue in MG).…”

Section: Expression Of Cd40l On T Cells Is Transient With the Ligandmentioning

confidence: 91%

Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus

Malheiros

Petzl-Erler

2009

Genes Immun

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Following the candidate gene approach we analyzed the CD40L, CD40, BLYS and CD19 genes that participate of B-cell co-stimulation, for association with pemphigus foliaceus (PF), an organ-specific autoimmune disease, characterized by the detachment of epidermal cells from each other (acantholysis) and presence of autoantibodies specific for desmoglein 1 (dsg1), an epidermal cell-adhesion molecule. The disease is endemic in certain regions of Brazil and also is known as fogo selvagem. Complex interactions among environmental and genetic susceptibility factors contribute to the manifestation of this multifactorial disease. The sample included 179 patients and 317 controls. Strong significant association was found with CD40LÀ726T4C (odds ratio, OR ¼ 5.54 and 0.30 for T þ and C þ genotypes, respectively). In addition, there were significant negative associations with CD40 À1T (OR ¼ 0.61) and BLYSÀ871T (OR ¼ 0.62) due to the decrease of the frequency of both homo-and heterozygotes in the patient group. No associations were found with variants of CD19 gene. Gene-gene interactions were observed between CD40 and BLYS, and between CD40L and BLYS. So, the dominant protective effects of CD40LÀ726C and of CD40 À1T only manifest in BLYSÀ871T þ individuals, and vice versa. We conclude that genetic variability of CD40L, CD40 and BLYS is an important factor for PF pathogenesis.

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Association of CD40 Gene Polymorphism (C-1T) with Susceptibility and Phenotype of Graves' Disease

Abstract: Our results support the notion that CD40 C-1T polymorphism has a modest effect on genetic susceptibility to sporadic GD.

Cited by 60 publications

References 38 publications

Association of single nucleotide polymorphism in CD28(C/T-I3 + 17) and CD40 (C/T-1) genes with the Graves disease

Association of single nucleotide polymorphism in CD28(C/T-I3 + 17) and CD40 (C/T-1) genes with the Graves disease

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

Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus

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