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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

Derived allele frequencies for six variants with minor allele frequencies in the CD40LG from French (FR) and Tunisian (TN) donors and those extracted from the 1000 genomes database.African Ancestry in Southwest US (ASW), Han Chinese in Beijing (CHB), Han Chinese South (CHS), Japanese individuals in Tokyo (JPT), Iberian populations in Spain (IBS), British from England and Scotland (GBR), Finnish from Finland (FIN), Utah residents with Northern and Western European ancestry (CEU), Tuscan in Italy (TSI), Colombian in Medellin (CLM), Puerto Rican in Puerto Rico (PUR), Mexican Ancestry in Los Angeles, CA (MXL), African Ancestry in Southwest US (ASW), Luhya in Webuye, Kenya (LWK), Africans “Yoruban in Ibadan”, Nigeria (YRI) taken from the 1000 genomes project. *Present study.
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f1: Derived allele frequencies for six variants with minor allele frequencies in the CD40LG from French (FR) and Tunisian (TN) donors and those extracted from the 1000 genomes database.African Ancestry in Southwest US (ASW), Han Chinese in Beijing (CHB), Han Chinese South (CHS), Japanese individuals in Tokyo (JPT), Iberian populations in Spain (IBS), British from England and Scotland (GBR), Finnish from Finland (FIN), Utah residents with Northern and Western European ancestry (CEU), Tuscan in Italy (TSI), Colombian in Medellin (CLM), Puerto Rican in Puerto Rico (PUR), Mexican Ancestry in Los Angeles, CA (MXL), African Ancestry in Southwest US (ASW), Luhya in Webuye, Kenya (LWK), Africans “Yoruban in Ibadan”, Nigeria (YRI) taken from the 1000 genomes project. *Present study.

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?
Derived allele frequencies for six variants with minor allele frequencies in the CD40LG from French (FR) and Tunisian (TN) donors and those extracted from the 1000 genomes database.African Ancestry in Southwest US (ASW), Han Chinese in Beijing (CHB), Han Chinese South (CHS), Japanese individuals in Tokyo (JPT), Iberian populations in Spain (IBS), British from England and Scotland (GBR), Finnish from Finland (FIN), Utah residents with Northern and Western European ancestry (CEU), Tuscan in Italy (TSI), Colombian in Medellin (CLM), Puerto Rican in Puerto Rico (PUR), Mexican Ancestry in Los Angeles, CA (MXL), African Ancestry in Southwest US (ASW), Luhya in Webuye, Kenya (LWK), Africans “Yoruban in Ibadan”, Nigeria (YRI) taken from the 1000 genomes project. *Present study.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Derived allele frequencies for six variants with minor allele frequencies in the CD40LG from French (FR) and Tunisian (TN) donors and those extracted from the 1000 genomes database.African Ancestry in Southwest US (ASW), Han Chinese in Beijing (CHB), Han Chinese South (CHS), Japanese individuals in Tokyo (JPT), Iberian populations in Spain (IBS), British from England and Scotland (GBR), Finnish from Finland (FIN), Utah residents with Northern and Western European ancestry (CEU), Tuscan in Italy (TSI), Colombian in Medellin (CLM), Puerto Rican in Puerto Rico (PUR), Mexican Ancestry in Los Angeles, CA (MXL), African Ancestry in Southwest US (ASW), Luhya in Webuye, Kenya (LWK), Africans “Yoruban in Ibadan”, Nigeria (YRI) taken from the 1000 genomes project. *Present study.
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