Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2.
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.
GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.|French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne 42023, France.
Chaker
C
Aloui
GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.|French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne 42023, France.
Antoine
A
Prigent
GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.
Sofiane
S
Tariket
GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.
Caroline
C
Sut
French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne 42023, France.
Jocelyne
J
Fagan
GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.|French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne 42023, France.
Fabrice
F
Cognasse
Regional Centre of Transfusion of Sousse, F. Hached University Hospital, Sousse 4000, Tunisia.
Tahar
T
Chakroun
GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.|National Institut of Blood Transfusion (INTS), Paris 75015, France.
Olivier
O
Garraud
GIMAP-EA3064, University of Lyon, Saint-Etienne 42023, France.|French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne 42023, France.
Sandrine
S
Laradi
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001792:Blood Platelets / Q000378:metabolism*; D019013:CD40 Antigens / Q000235:genetics*; D023201:CD40 Ligand / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D019013:CD40 Antigens; D039421:Integrin alpha2; D023201:CD40 Ligand