DAAM2 polymorphism is closely related to the clinical outcomes of allogeneic hematopoietic stem cell transplantation

Ann Hematol. 2012 Apr;91(4):571-6. doi: 10.1007/s00277-011-1325-x. Epub 2011 Sep 10.

Abstract

Disheveled associated activator of morphogenesis 2 (DAAM2) is one of the key proteins of WNT/plantar cell polarity signaling pathway which is closely linked to oncogenesis, cellular proliferation and regeneration, and stem cell renewal. This study investigated the association of DAAM2 genetic polymorphism with the clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We selected candidate single nucleotide polymorphisms (SNPs) by DNA chip analysis using Illumina Infinium Human-1 microarrays™ on 15 patients who underwent allogeneic HSCT with (N = 7) or without (N = 8) acute graft versus host disease (GvHD). Six SNPs (rs2504787, rs2504086, rs2504082, rs3004067, rs882559, and rs3004070) of DAAM2 were associated with acute GvHD prevalence, and the genotyping was extended to larger population (N = 228). Medical records were reviewed to see the correlation of these SNPs with the clinical outcomes of the patients. In rs2504082 and rs882559, treatment-related mortality was significantly lower in major homozygote than other genotypes (29.3% in AA vs. 44.3% in AG or GG, p = 0.0214; 23.0% in CC vs. 39.9% in CG or GG, p = 0.0072, respectively). Acute GvHD incidence and engraftment time were significantly different according to the specific genotype of selected SNPS in this study. This study is the first report regarding the clinical value of DAAM2 polymorphism as a predictive marker of clinical outcomes of allogeneic HSCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Disease-Free Survival
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Hematologic Diseases / surgery
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphoproliferative Disorders / surgery
  • Male
  • Microfilament Proteins
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult
  • rho GTP-Binding Proteins

Substances

  • DAAM2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • rho GTP-Binding Proteins