Genetic association of interleukin-1beta and receptor antagonist (IL-1Ra) gene polymorphism with allograft function in renal transplant patients. 2006

Parmeet Kaur Manchanda, and Hemant Kumar Bid, and Anant Kumar, and Rama Devi Mittal
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.

Cytokines are known to be important mediators during renal graft outcome. The present study was therefore, conducted to determine the impact of IL-1beta and its receptor antagonist polymorphism on allograft outcome. We evaluated single nucleotide polymorphism (SNPs) in interleukin-1 gene cluster, IL-1beta (promoter region -511 and exon-5 +3954) and IL-1Ra (86-bp VNTR) in 136 renal transplant recipients and 150 normal healthy controls by polymerase chain restriction based (PCR-RFLP) analysis. Recipients were HLA matched and clinically characterized including delayed graft function (DGF), rejection episode (RE) and stable graft function (SGF). Haplotypes and linkage disequilibrium (LD) were determined using SNPAnalyzer software. Significant difference was observed for the frequency distribution of the three sites of IL-1 gene among patients and controls (p<0.001, 0.022 and <0.001 respectively). When RE and DGF were compared to SGF, only IL-1Ra showed significant differences among RE and SGF (p=0.014) and DGF and SGF (p=0.020). The presence of 1/2 genotype showed 18 folds risk in RE and 10 folds in DGF (OR=18.000 and OR=10.667 respectively). The majority of recipients with SGF had 1-4 HLA mismatch whereas RE had 5-8 mismatches. Risk for rejection increased >6 folds (OR=6.571; p<0.01) for 5-8 mismatches. Haplotypes constructed with the combination of three polymorphisms in IL-1 gene cluster showed significant difference between RE and SGF group. LD value for IL-1beta (promoter region) and IL-1Ra and IL-1beta promoter and exon-5 gene in the control group indicated strong association among the variants (D'=0.37, p<0.0001 and D'=0.29, p=0.002). Our study demonstrate that genetically determined low production of IL-1Ra may be a risk factor for RE and DGF and that IL-1beta/IL-1Ra haplotype influences the impact of allograft outcome. These findings may significantly abet in better perception of the survival of the graft.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D005260 Female Females
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype
D006650 Histocompatibility Testing Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed) Crossmatching, Tissue,HLA Typing,Tissue Typing,Crossmatchings, Tissue,HLA Typings,Histocompatibility Testings,Testing, Histocompatibility,Testings, Histocompatibility,Tissue Crossmatching,Tissue Crossmatchings,Tissue Typings,Typing, HLA,Typing, Tissue,Typings, HLA,Typings, Tissue
D006683 HLA-DQ Antigens A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases. HLA-DC Antigens,HLA-MB Antigens,HLA-DC,HLA-DQ,HLA-DS,HLA-DS Antigens,HLA-LB,HLA-LB Antigens,HLA-MB,Antigens, HLA-DC,Antigens, HLA-DQ,Antigens, HLA-DS,Antigens, HLA-LB,Antigens, HLA-MB,HLA DC Antigens,HLA DQ Antigens,HLA DS Antigens,HLA LB Antigens,HLA MB Antigens

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