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P2X₇ receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation

From the Department of Internal Medicine (K-HL, IK, S-SY, SP, BKK); Department of Laboratory Medicine (SSP, EKR); Department of Preventive Medicine, Seoul National University, College of Medicine, Seoul, Korea (JHK, Y-CH); Diagnostic DNA Chip Center, The Ilchun Molecular Medicine Institute, Medical Research Center, Seoul National University, College of Medicine, Seoul, Korea (IK, SP); Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Korea (IK, S-SY, SP, BKK)

Correspondence: Inho Kim, Professor Department of Internal Medicine, Seoul National University College of Medicine 28 Yongon-Dong, Chongno-Gu Seoul, 110-744, Korea. E-mail: kim_dajung{at}hanmail.net

Background and Objectives: 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.

Design and 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).

Interpretation and 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.

Key words: P2X₇, polymorphism, hematopoietic stem cell transplantation, IL-1, IL-18.

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