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Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?

View Article: PubMed Central - PubMed

ABSTRACT

The CD40 ligand (CD40L/CD154), a member of TNF superfamily, is notably expressed on activated CD4+ T-cells and stimulated platelets. CD40L is linked to a variety of pathologies and to acute transfusion reactions (ATR). Mutations in this gene (CD40LG) lead to X-linked hyper-IgM syndrome. Some CD40LG polymorphisms are associated with variable protein expression. The rationale behind this study is that CD40L protein has been observed to be involved in ATR. We wondered whether genetic polymorphisms are implicated. We investigated genetic diversity in the CD40LG using DHPLC and capillary electrophoresis for screening and genotyping (n = 485 French and Tunisian blood donors). We identified significant difference in the CD40LG linkage pattern between the two populations. Variant minor alleles were significantly over-represented in Tunisian donors (P<0.0001 to 0.0270). We found higher heterogeneity in the Tunisian, including three novel low frequency variants. As there was not a particular pattern of CD40LG in single apheresis donors whose platelet components induced an ATR, we discuss how this information may be useful for future disease association studies on CD40LG.

No MeSH data available.


Related in: MedlinePlus

Genomic structure of the CD40LG and the haplotype blocks of the French (FR) and Tunisian (TN) populations (this study) compared with those of JPT, CEU, YRI and TSI (HapMap data).(a) Genomic structure of the CD40LG gene and the position of the identified polymorphisms. Exons are represented by boxes, with filled boxes denoting translated regions. Upward facing lines indicate amplified fragments, and polymorphisms are shown as red stars for SNPs and purple lozenges for microsatellites. (b) CD40LG LD and haplotype diversity in French and Tunisian populations. (c) CD40LG LD and haplotype diversity in JPT, CEU, YRI and TSI populations. The numbers in boxes represent the pairwise D’ value between adjacent SNPs. For (b) and (c), haplotype frequencies are shown below the LD diagrams. Triangular pointers highlight SNPs which could be tagged for future association analysis.
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f2: Genomic structure of the CD40LG and the haplotype blocks of the French (FR) and Tunisian (TN) populations (this study) compared with those of JPT, CEU, YRI and TSI (HapMap data).(a) Genomic structure of the CD40LG gene and the position of the identified polymorphisms. Exons are represented by boxes, with filled boxes denoting translated regions. Upward facing lines indicate amplified fragments, and polymorphisms are shown as red stars for SNPs and purple lozenges for microsatellites. (b) CD40LG LD and haplotype diversity in French and Tunisian populations. (c) CD40LG LD and haplotype diversity in JPT, CEU, YRI and TSI populations. The numbers in boxes represent the pairwise D’ value between adjacent SNPs. For (b) and (c), haplotype frequencies are shown below the LD diagrams. Triangular pointers highlight SNPs which could be tagged for future association analysis.

Mentions: Variant minor alleles with MAF>0.05 were significantly over-represented in the Tunisian individuals (P<0.0001 to 0.027), in comparison with the French individuals (Table 1). In addition, we compared MAFs for the two populations with those extracted from the 1000 genomes project (Figure 1). In the present French population, all the allele frequencies were close to those belonging to the Utah residents with Northern and Western European ancestry (CEU) population (Figure 2). Regarding the Tunisian study, all the allele frequencies of the SNPs fell between those belonging to African ancestry (African Ancestry in Southwest US, ASW; Luhya in Webuye, Kenya, LWK; Africans “Yoruban in Ibadan”, Nigeria, YRI) and those with European origins, the CEU group, British from England and Scotland (GBR) and Tuscan in Italy (TSI), with the exception of rs1126535 for which the frequency is very close to that of TSI.


Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?
Genomic structure of the CD40LG and the haplotype blocks of the French (FR) and Tunisian (TN) populations (this study) compared with those of JPT, CEU, YRI and TSI (HapMap data).(a) Genomic structure of the CD40LG gene and the position of the identified polymorphisms. Exons are represented by boxes, with filled boxes denoting translated regions. Upward facing lines indicate amplified fragments, and polymorphisms are shown as red stars for SNPs and purple lozenges for microsatellites. (b) CD40LG LD and haplotype diversity in French and Tunisian populations. (c) CD40LG LD and haplotype diversity in JPT, CEU, YRI and TSI populations. The numbers in boxes represent the pairwise D’ value between adjacent SNPs. For (b) and (c), haplotype frequencies are shown below the LD diagrams. Triangular pointers highlight SNPs which could be tagged for future association analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384113&req=5

f2: Genomic structure of the CD40LG and the haplotype blocks of the French (FR) and Tunisian (TN) populations (this study) compared with those of JPT, CEU, YRI and TSI (HapMap data).(a) Genomic structure of the CD40LG gene and the position of the identified polymorphisms. Exons are represented by boxes, with filled boxes denoting translated regions. Upward facing lines indicate amplified fragments, and polymorphisms are shown as red stars for SNPs and purple lozenges for microsatellites. (b) CD40LG LD and haplotype diversity in French and Tunisian populations. (c) CD40LG LD and haplotype diversity in JPT, CEU, YRI and TSI populations. The numbers in boxes represent the pairwise D’ value between adjacent SNPs. For (b) and (c), haplotype frequencies are shown below the LD diagrams. Triangular pointers highlight SNPs which could be tagged for future association analysis.
Mentions: Variant minor alleles with MAF>0.05 were significantly over-represented in the Tunisian individuals (P<0.0001 to 0.027), in comparison with the French individuals (Table 1). In addition, we compared MAFs for the two populations with those extracted from the 1000 genomes project (Figure 1). In the present French population, all the allele frequencies were close to those belonging to the Utah residents with Northern and Western European ancestry (CEU) population (Figure 2). Regarding the Tunisian study, all the allele frequencies of the SNPs fell between those belonging to African ancestry (African Ancestry in Southwest US, ASW; Luhya in Webuye, Kenya, LWK; Africans “Yoruban in Ibadan”, Nigeria, YRI) and those with European origins, the CEU group, British from England and Scotland (GBR) and Tuscan in Italy (TSI), with the exception of rs1126535 for which the frequency is very close to that of TSI.

View Article: PubMed Central - PubMed

ABSTRACT

The CD40 ligand (CD40L/CD154), a member of TNF superfamily, is notably expressed on activated CD4+ T-cells and stimulated platelets. CD40L is linked to a variety of pathologies and to acute transfusion reactions (ATR). Mutations in this gene (CD40LG) lead to X-linked hyper-IgM syndrome. Some CD40LG polymorphisms are associated with variable protein expression. The rationale behind this study is that CD40L protein has been observed to be involved in ATR. We wondered whether genetic polymorphisms are implicated. We investigated genetic diversity in the CD40LG using DHPLC and capillary electrophoresis for screening and genotyping (n = 485 French and Tunisian blood donors). We identified significant difference in the CD40LG linkage pattern between the two populations. Variant minor alleles were significantly over-represented in Tunisian donors (P&lt;0.0001 to 0.0270). We found higher heterogeneity in the Tunisian, including three novel low frequency variants. As there was not a particular pattern of CD40LG in single apheresis donors whose platelet components induced an ATR, we discuss how this information may be useful for future disease association studies on CD40LG.

No MeSH data available.


Related in: MedlinePlus