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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-4-25
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0966-3274
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-96
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16635751-Adolescent, pubmed-meshheading:16635751-Adult, pubmed-meshheading:16635751-Delayed Graft Function, pubmed-meshheading:16635751-Female, pubmed-meshheading:16635751-Graft Rejection, pubmed-meshheading:16635751-Graft Survival, pubmed-meshheading:16635751-HLA-A Antigens, pubmed-meshheading:16635751-HLA-B Antigens, pubmed-meshheading:16635751-HLA-DQ Antigens, pubmed-meshheading:16635751-HLA-DR Antigens, pubmed-meshheading:16635751-Haplotypes, pubmed-meshheading:16635751-Histocompatibility Testing, pubmed-meshheading:16635751-Humans, pubmed-meshheading:16635751-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:16635751-Interleukin-1, pubmed-meshheading:16635751-Kidney Transplantation, pubmed-meshheading:16635751-Linkage Disequilibrium, pubmed-meshheading:16635751-Male, pubmed-meshheading:16635751-Middle Aged, pubmed-meshheading:16635751-Minisatellite Repeats, pubmed-meshheading:16635751-Polymorphism, Genetic, pubmed-meshheading:16635751-Sialoglycoproteins
pubmed:year
2006
pubmed:articleTitle
Genetic association of interleukin-1beta and receptor antagonist (IL-1Ra) gene polymorphism with allograft function in renal transplant patients.
pubmed:affiliation
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't