Transcriptional Activity of the Distal CD40 Ligand Promoter

Lobo, Francis; Xu, Sheng; Lee, Celine; Fuleihan, Ramsay

doi:10.1006/bbrc.2000.3914

Cited by 17 publications

(19 citation statements)

References 41 publications

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“…In the 5 0 region of CD40L there are three putative NFAT transcription factor binding sites, the most distal one being about 760 bp upstream of the transcription start site. 33 If this variation can change affinity of these proteins needs to be clarified. Regarding the microsatellite in 3 0 UTR of CD40L, Citores et al 34 demonstrated that the group of longer alleles is associated with SLE, accompanied by a more prolonged protein expression in activated lymphocytes from controls.…”

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

confidence: 99%

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

confidence: 99%

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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“…In the 5 0 -flanking region, there are three NFAT transcription factor-binding sites, the most distal one being about 760 bp upstream of the transcription start site. 21 Again, no variation likely to be involved in transcriptional factor binding was identified despite extensive screening.…”

Section: Discussionmentioning

confidence: 99%

“…A total of 22 SNPs were identified by sequencing the entire CD40L gene (12.2 kb), including the 3.4 kb 5 0 upstream region that includes the previously described promoter, 21 and all five exons and introns ( Figure 1 and Table 1). In all, 12 of the 22 SNPs were identical to those in the dbSNP database (http://www.ncbi.nlm.nih.gov/entrez/ query.fcgi?db ¼ snp).…”

Section: Identification Of Variations In Cd40lmentioning

confidence: 99%

CD40 ligand gene and Kawasaki disease

Onouchi¹,

Onoue²,

Tamari³

et al. 2004

Eur J Hum Genet

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Kawasaki disease (KD) is an acute systemic vasculitis syndrome of infants and young children. Although its etiology is largely unknown, epidemiological findings suggest that genetic factors play a role in the pathogenesis of KD. To identify genetic factors, affected sib-pair analysis has been performed. One of the identified peaks was located on the Xq26 region. A recent report of elevated expression of CD40 ligand (CD40L), which maps to Xq26, during the acute-phase KD, and its relationship to the development of coronary artery lesions (CAL) prompted us to screen for polymorphism of CD40L and to study the association of the gene to KD. A newly identified SNP in intron 4 (IVS4 þ 121 A4G) is marginally overrepresented in KD patients as compared to controls (109/602, 18.1 vs 111/737, 15.1%). When male KD patients with CAL were analyzed as a patient group, the SNP was significantly more frequent than in controls (15/58, 25.9%, vs 111/737, 15.1%, OR ¼ 2.0, 95% CI ¼ 1.07 -3.66; P ¼ 0.030). Interestingly, this variation was extremely rare in a control Caucasian population (1/145, 0.7%). Our results suggest a role of CD40L in the pathogenesis of CAL and might explain the excess of males affected with KD.

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“…18 The 6xNF-kB CD40L/TKm reporter was obtained by cloning 6 copies of the NF-kB binding site (5Ј-AGGGATT-TCCA-3Ј) of the CD40L promoter upstream of the minimal thymidine kinase promoter in the pGL3 luciferase reporter plasmid (a gift from Dr Peter Vandenberghe, Laboratory for Experimental Hematology, University of Leuven, Belgium). 19 Site-directed mutagenesis of pGL3-CD154-luc at the distal B site (Ϫ1180, from AGGGATTTCC to AGCCAAGTCC) and the NFAT2 site (Ϫ250, from TAGGAAAATA to TACCACCATA) (mutated residues are underlined) was performed using the QuikChange multisitedirected mutagenesis kit from Stratagene (La Jolla, CA).…”

Section: Plasmids and Site-directed Mutagenesismentioning

confidence: 99%