Lee Kyung-Hun, Park Sung Sup, Kim Inho, Kim Jin Hee, Ra Eun Kyung, Yoon Sung-Soo, Hong Yun-Chul, Park Seonyang, Kim Byoung Kook
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Haematologica. 2007 May;92(5):651-7. doi: 10.3324/haematol.10810.
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.
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.
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 1.835.77) and a donor 1513CC genotype (hazard ratio 2.66, 95% confidence interval 1.026.91) 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).
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.
P2X7受体（P2X7R）在白细胞介素（IL）-1的加工与释放过程中起关键作用。为评估P2X7R基因的A1513C多态性是否与异基因干细胞移植结局相关，我们对接受人类白细胞抗原（HLA）匹配同胞干细胞移植患者的该多态性与临床结局进行了关联分析。
152例患有恶性肿瘤或再生障碍性贫血的患者在单一机构接受异基因干细胞移植。对这152例患者及其152名供者的外周血DNA进行基因分型。获取145例受者和150例供者的基因型并分析该多态性。
在所有295名研究对象中，A和C等位基因频率分别为72%和28%。患者的基因型为AA型75例、AC型58例、CC型12例；供者的基因型为AA型74例、AC型70例、CC型6例。CC基因型受者的总生存期显著短于AA或AC基因型受者（1513CC型为92天，1513AA或1513AC型为821天，p = 0.012），且CC基因型供者的受者总生存期短于AA或AC基因型供者的受者（1513CC型为63天，1513AA或1513AC型为702天，p = 0.024）。多因素分析将高危组（风险比3.25，95%置信区间1.835.77）和供者1513CC基因型（风险比2.66，95%置信区间1.026.91）确定为生存期较短的危险因素，分析参数包括性别、年龄、移植方法（减低剂量预处理与传统预处理）、干细胞来源、风险组以及P2X7R受者和供者基因型。微生物学证实的菌血症在CC供者基因型受者中发生率为66.7%，在AA或AC基因型移植受者中发生率为17.6%（p = 0.014）。
我们得出结论，P2X7R基因中的A1513C多态性与异基因干细胞移植后感染的发生及生存情况相关。因此，检测该多态性可能有助于优化患者和供者的选择。
