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Review
. 2012 May 31;119(22):5311-9.
doi: 10.1182/blood-2011-09-371153. Epub 2012 Jan 26.

Evaluation of published single nucleotide polymorphisms associated with acute GVHD

Jason W Chien  1 , Xinyi Cindy Zhang, Wenhong Fan, Hongwei Wang, Lue Ping Zhao, Paul J Martin, Barry E Storer, Michael Boeckh, Edus H Warren, John A Hansen
Affiliations
Review

Evaluation of published single nucleotide polymorphisms associated with acute GVHD

Jason W Chien et al. Blood. .

Abstract

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.

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Figures

Figure 1
Figure 1
Candidate SNP genotype determination algorithm. HWE indicates Hardy-Weinberg equilibrium; MAF, minor allele frequency; and SNP, single-nucleotide polymorphism.
Figure 2
Figure 2
Forest plots for unadjusted and adjusted analyses of aGVHD and candidate SNPs. Forest plots for unadjusted (squares) and adjusted (circles) analyses of aGVHD and candidate SNPs among MRD (A) and URD (B) HCT. Hazard ratios are represented on the x-axis in logarithmic scale. Positive values indicate an increased risk for aGVHD, and negative values indicate a decreased risk for aGVHD. Gene/rs numbers in bold and closed squares and circles indicate the association exceeded the P = .05 threshold.
See this image and copyright information in PMC

Comment in

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