Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2
| Autor: | Tahar Chakroun, Olivier Garraud, Chaker Aloui, Fabrice Cognasse, Sofiane Tariket, Sandrine Laradi, Antoine Prigent, Caroline Sut, Jocelyne Fagan |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Blood Platelets Male 0301 basic medicine medicine.medical_specialty Adolescent CD40 Ligand Integrin alpha2 Human platelet 030204 cardiovascular system & hematology Polymorphism Single Nucleotide Article Linkage Disequilibrium Young Adult 03 medical and health sciences 0302 clinical medicine Gene Frequency Internal medicine Humans Medicine Platelet Secretion CD40 Antigens Allele Soluble cd40l Gene Alleles Genetics Multidisciplinary CD40 biology business.industry Haplotype 030104 developmental biology Endocrinology Haplotypes biology.protein Female business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep24715 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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