Park Ji In, Yang Seung Hee, Lee Jung Pyo, Yoo Seong Ho, Kim Yon Su
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Kidney Res Clin Pract. 2015 Mar;34(1):47-52. doi: 10.1016/j.krcp.2015.01.002. Epub 2015 Jan 28.
Aquaporin-11 (AQP11) is a novel member of the aquaporin family. Disruption of the murine Aqp11 gene causes severe proximal tubular injury and renal failure. The rs2276415 (G>A) single-nucleotide polymorphism in the human AQP11 gene results in glycine to serine substitution in a functionally important domain. In this study, the role of the genetic predispositions of AQP11 rs2276415 (G>A) on renal allograft outcomes was evaluated.
A total of 198 pairs of donors and recipients were enrolled in this study. Long-term graft survival was traced and clinical parameters that could have influenced graft outcome were collected through the electronic medical record system.
The genotype distribution and allele frequency of rs2276415 polymorphism were not different between donors and recipients. Despite similar allele frequencies between donors and recipients, the minor allele rs2276415 (GA+AA) of AQP11 from the donors, but not from the recipients, had a harmful effect on the graft survival compared with the wild-type donor (GG; P=0.029). This association was significant after adjusting for several risk factors including age, sex, human leukocyte antigen mismatch, donor type, hypertension, and diabetes mellitus (P=0.032).
A donor-derived, not recipient-derived, genetic AQP11 polymorphism has different effects on graft outcome. Thus, the genetic influence from donors should be carefully considered for proper management of allografts after kidney transplantation.
水通道蛋白11(AQP11)是水通道蛋白家族的一个新成员。小鼠Aqp11基因的破坏会导致严重的近端肾小管损伤和肾衰竭。人类AQP11基因中的rs2276415(G>A)单核苷酸多态性导致在一个功能重要结构域中甘氨酸被丝氨酸取代。在本研究中,评估了AQP11 rs2276415(G>A)基因易感性对肾移植结果的作用。
本研究共纳入198对供体和受体。追踪长期移植物存活情况,并通过电子病历系统收集可能影响移植物结果的临床参数。
rs2276415多态性的基因型分布和等位基因频率在供体和受体之间没有差异。尽管供体和受体之间的等位基因频率相似,但与野生型供体(GG;P=0.029)相比,来自供体而非受体的AQP11次要等位基因rs2276415(GA+AA)对移植物存活有有害影响。在调整包括年龄、性别、人类白细胞抗原错配、供体类型、高血压和糖尿病等多个风险因素后,这种关联仍然显著(P=0.032)。
供体来源而非受体来源的AQP11基因多态性对移植物结果有不同影响。因此,在肾移植后对同种异体移植物进行适当管理时,应仔细考虑供体的遗传影响。