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Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2.

Aloui C, Prigent A, Tariket S, Sut C, Fagan J, Cognasse F, Chakroun T, Garraud O, Laradi S - Sci Rep (2016)

Bottom Line: One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009).Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components.Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings.

View Article: PubMed Central - PubMed

Affiliation: GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.

ABSTRACT
Increased circulating soluble CD40 ligand (sCD40L) is commonly associated with inflammatory disorders. We aimed to investigate whether gene polymorphisms in CD40LG, CD40 and ITGA2 are associated with a propensity to secrete sCD40L; thus, we examined this issue at the level of human platelets, the principal source of sCD40L. We performed single polymorphism and haplotype analyses to test for the effect of twelve polymorphisms across the CD40LG, CD40 and ITGA2 genes in blood donors. ITGA2 presented a positive association with rs1126643, with a significant modification in sCD40L secretion (carriers of C allele, P =  0.02), unlike the investigated CD40LG and CD40 polymorphisms. One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009). The sCD40L level was associated with the inter-chromosomal CD40LG/CD40/ITGA2 haplotype (ATC), displaying rs3092952 (A/G), rs1883832 (C/T) and rs1126643 (C/T), with increased sCD40L levels (P = 0.0135). Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components. Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings.

No MeSH data available.


Related in: MedlinePlus

Representative LD plot of the two haplotype blocks at CD40LG and the tagged SNPs used for the haplotype association.
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f1: Representative LD plot of the two haplotype blocks at CD40LG and the tagged SNPs used for the haplotype association.

Mentions: For haplotype association, we used Haploview 4.2 software and employed the algorithm proposed by Gabriel41 in order to choose tagged SNPs based on our previous study16. The haplotype tagger function was used to identify redundant SNPs, which were considered redundant if the pairwise LD (r2) was ≥0.8. Haplotypes with a frequency ≤1% were excluded from the analysis (Fig. 1).


Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2.

Aloui C, Prigent A, Tariket S, Sut C, Fagan J, Cognasse F, Chakroun T, Garraud O, Laradi S - Sci Rep (2016)

Representative LD plot of the two haplotype blocks at CD40LG and the tagged SNPs used for the haplotype association.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837387&req=5

f1: Representative LD plot of the two haplotype blocks at CD40LG and the tagged SNPs used for the haplotype association.
Mentions: For haplotype association, we used Haploview 4.2 software and employed the algorithm proposed by Gabriel41 in order to choose tagged SNPs based on our previous study16. The haplotype tagger function was used to identify redundant SNPs, which were considered redundant if the pairwise LD (r2) was ≥0.8. Haplotypes with a frequency ≤1% were excluded from the analysis (Fig. 1).

Bottom Line: One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009).Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components.Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings.

View Article: PubMed Central - PubMed

Affiliation: GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.

ABSTRACT
Increased circulating soluble CD40 ligand (sCD40L) is commonly associated with inflammatory disorders. We aimed to investigate whether gene polymorphisms in CD40LG, CD40 and ITGA2 are associated with a propensity to secrete sCD40L; thus, we examined this issue at the level of human platelets, the principal source of sCD40L. We performed single polymorphism and haplotype analyses to test for the effect of twelve polymorphisms across the CD40LG, CD40 and ITGA2 genes in blood donors. ITGA2 presented a positive association with rs1126643, with a significant modification in sCD40L secretion (carriers of C allele, P =  0.02), unlike the investigated CD40LG and CD40 polymorphisms. One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009). The sCD40L level was associated with the inter-chromosomal CD40LG/CD40/ITGA2 haplotype (ATC), displaying rs3092952 (A/G), rs1883832 (C/T) and rs1126643 (C/T), with increased sCD40L levels (P = 0.0135). Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components. Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings.

No MeSH data available.


Related in: MedlinePlus