Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Blood. 2012 May 31;119(22):5311-9. doi: 10.1182/blood-2011-09-371153. Epub 2012 Jan 26.
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.
候选基因与急性移植物抗宿主病（aGVHD）的关联采用全基因组扫描的 1298 名异基因造血细胞移植（HCT）供体和受者的基因分型和推断的单核苷酸多态性数据进行评估。在 40 个先前报道的候选 SNP 中，有 6 个成功进行了基因分型，有 10 个进行了推断并通过了分析标准。对患者和供体基因型进行了评估，以关联 IIb-IV 级和 III-IV 级 aGVHD，按供体类型进行分层，在单变量和多变量等位、隐性和显性模型中进行评估。使用推断的基因型来复制先前的 IL10 关联得到了验证。与先前的出版物相似，rs1800795 的供体 IL6 基因型与无关 HCT 后 IIb-IV 级 aGVHD 的风险增加 20%-50%相关，在等位（调整 P =.011）和隐性（调整 P =.0013）模型中。供体基因型与相关 HCT 后 III-IV 级 aGVHD 的风险增加 60%相关（调整 P =.028）。还发现了其他与 IL2、CTLA4、HPSE 和 MTHFR 相关的关联，但与原始出版物不一致。这些结果说明了在遗传分析中使用推断的单核苷酸多态性数据的优势，并证明了遗传关联研究中验证的重要性。
