Protein Z polymorphisms associated with vaso-occlusive crisis in young sickle cell disease patients

Ann Hematol. 2012 Aug;91(8):1215-20. doi: 10.1007/s00277-012-1474-6. Epub 2012 May 11.


We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) vaso-occlusive crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P=0.03), rs3024719 (P=0.02), rs3024731 (P<0.001), and rs3024735 (P<0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P=0.028) and rs3024735 (P=0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P=0.024), AGAA (P=0.011), and GGTG (P=0.002), and reduced frequency of AGTG haplotype (P=0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (P(c)=0.001) and GGTG (P(c)=0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / genetics*
  • Arterial Occlusive Diseases / complications
  • Arterial Occlusive Diseases / genetics*
  • Blood Proteins / genetics*
  • Child
  • Child, Preschool
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Polymorphism, Genetic* / physiology
  • Vascular Diseases / complications
  • Vascular Diseases / genetics
  • Young Adult


  • Blood Proteins
  • plasma protein Z