ارتباط بين چند شكلي ژن IL-1Ra در دهنده و گيرنده پيوند مغز استخوان با بيماري پيوند عليه ميزبان به عنوان يك عامل پيش آگهي دهنده

Relationship between IL-1Ra gene polymorphism and GVHD as a prognostic factor

Background and Objectives GVHD occurs in 20-40% of recipients of HLA-matched sibling donor grafts. A number of studies suggest that polymorphism in cytokine genes influence susceptibility to post-BMT complications. One of the cytokine gene family (IL-1RN) encodes IL-1 receptor antagonist (IL-1Ra), an anti-inflammatory molecule that competes for receptor binding with IL-1 a and IL-1J. The overall contribution of IL-1 to the proinflammatory response depends on the balance between these three molecules. In this study, we decided to evaluate the polymorphisms of IL-1Ra gene that might influence the outcome of BMT. Materials and Methods In this cohort study, patientsʹ (n = 175) and donorsʹ (n = 175) DNA from a total of 350 human leucocyte antigen (HLA)-identical sibling allogeneic BMTs were analysed. IL-1Ra gene polymorphism was studied by PCR-VNTR method. PCR products were then visualized by electrophoresis in 2% agarose gel. Then, the correlation between donor and recipient genotype and GVHD grade for their respective transplant was assessed. Results The frequency of the aGVHD grades was divided to grade 0 (38.3%), grade I (17.7%), grade II (27.4%), grade III (13.7%), grade IV (2.9%). Correlation between donor and recipient genotype and GVHD grade for their respective transplant was assessed. We observed no significant correlation between the IL-1Ra polymorphism and incidence of aGVHD, although possession of the allele 2 in the individual genotype was associated with less severe acute GVHD. Conclusions The observed allele frequencies were different from those previously reported. None of the polymorphisms showed association with the presence of acute GVHD. However, presence of allele 2 showed association with aGVHD. If the recipient possesed allele 2, the probability of aGVHD was 46% and in the absence of allele 2, it was 62%. Recipient age, donor age, recipient disease particularly thalassemia were the most remarkable risk factors for acute GVHD.