title: P2X7 receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  The P2X7 receptor (P2X7 R) is a key player in the processing and release of interleukin (IL)-1. To evaluate whether the A1513C polymorphism of the P2X7 R gene is related to allogeneic stem cell transplantation outcome, we performed an association analysis between this polymorphism and clinical outcomes in patients treated with an HLA-matched sibling stem cell transplant.
  
  
  METHODS
  Patients (n=152) with a malignancy or aplastic anemia underwent allogeneic stem cell transplantation at a single institute. Peripheral blood DNA of these 152 patients and their 152 donors was genotyped. Genotypes of 145 recipients and 150 donors were obtained and analyzed for the polymorphism.
  
  
  RESULTS
  The frequencies of the A and C alleles in all 295 study subjects were 72% and 28%, respectively. The genotypes in patients were AA in 75, AC in 58, and CC in 12; the genotypes in donors were AA in 74, AC in 70, and CC in 6. Overall survival was significantly shorter for recipients with the CC genotype than for those with the AA or AC genotype (92 days for 1513CC vs. 821 days for 1513AA or 1513AC, p=0.012), and for recipients from donors with the CC genotype than for recipients from donors with the AA or AC genotype (63 days for 1513CC vs. 702 days for 1513AA or 1513AC, p=0.024). Multivariate analyses, which included sex, age, transplant method (reduced intensity conditioning vs. conventional conditioning), stem cell source, risk group, and P2X7R recipient and donor genotypes, as parameters, identified high-risk group (hazard ratio 3.25, 95% confidence interval 1.83~5.77) and a donor 1513CC genotype (hazard ratio 2.66, 95% confidence interval 1.02~6.91) as risk factors for a shorter survival. Microbiologically documented bacteremia occurred in 66.7% of recipients with the CC donor genotype and in 17.6% of recipients of transplants of AA or AC genotype (p=0.014).
  
  
  CONCLUSIONS
  We conclude that the A1513C polymorphism in the P2X7R gene is related to the occurrence of infections and survival after allogeneic stem cell transplantation. Thus, the determination of this polymorphism may be helpful for the optimal selection of patients and donors.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Ra
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Yun-Chul
authors.initials: YC
authors.lastname: Hong
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.forename: Byoung Kook
authors.initials: BK
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000401:mortality / Q000601:surgery; D016470:Bacteremia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D019337:Hematologic Neoplasms / Q000401:mortality / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality / Q000706:statistics & numerical data; D006801:Humans; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology*; D018048:Receptors, Purinergic P2 / Q000032:analysis / Q000235:genetics*; D058486:Receptors, Purinergic P2X7; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D014184:Transplantation, Homologous / Q000401:mortality / Q000706:statistics & numerical data; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7