Evaluation of published single nucleotide polymorphisms associated with acute GVHD
| Autor: | Barry E. Storer, Jason W. Chien, Xinyi Cindy Zhang, Edus H. Warren, Hongwei Wang, Wenhong Fan, Lue Ping Zhao, Paul J. Martin, Michael Boeckh, John A. Hansen |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Oncology Male medicine.medical_specialty Genotype medicine.medical_treatment Immunology Graft vs Host Disease Single-nucleotide polymorphism Hematopoietic stem cell transplantation Biology Biochemistry Polymorphism Single Nucleotide Polymorphism (computer science) immune system diseases Internal medicine medicine Transplantation Homologous Humans Genetic Predisposition to Disease Allele Alleles Methylenetetrahydrofolate Reductase (NADPH2) Genetic association Glucuronidase Transplantation Interleukin-6 Hematopoietic Stem Cell Transplantation Cell Biology Hematology Middle Aged Interleukin-10 surgical procedures operative Methylenetetrahydrofolate reductase Acute Disease biology.protein Interleukin-2 Female |
| Popis: | Candidate genetic associations with acute GVHD (aGVHD) were evaluated with the use of genotyped and imputed single-nucleotide polymorphism data from genome-wide scans of 1298 allogeneic hematopoietic cell transplantation (HCT) donors and recipients. Of 40 previously reported candidate SNPs, 6 were successfully genotyped, and 10 were imputed and passed criteria for analysis. Patient and donor genotypes were assessed for association with grades IIb-IV and III-IV aGVHD, stratified by donor type, in univariate and multivariate allelic, recessive and dominant models. Use of imputed genotypes to replicate previous IL10 associations was validated. Similar to previous publications, the IL6 donor genotype for rs1800795 was associated with a 20%-50% increased risk for grade IIb-IV aGVHD after unrelated HCT in the allelic (adjusted P = .011) and recessive (adjusted P = .0013) models. The donor genotype was associated with a 60% increase in risk for grade III-IV aGVHD after related HCT (adjusted P = .028). Other associations were found for IL2, CTLA4, HPSE, and MTHFR but were inconsistent with original publications. These results illustrate the advantages of using imputed single-nucleotide polymorphism data in genetic analyses and demonstrate the importance of validation in genetic association studies. |
| Databáze: | OpenAIRE |
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