Neri Andrea, Scalzotto Elisa, Corradi Valentina, Caprara Carlotta, Salin Alberto, Cannone Manuela, De Cal Massimo, Romano Giulio, Tulissi Patrizia, Cussigh Anna Rosa, Montanaro Domenico, Frigo Annachiara, Giavarina Davide, Chiaramonte Stefano, Ronco Claudio
Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy.
Specialist Biologist in Genetics, Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), ULSS 8 BERICA, San Bortolo Hospital, San Bortolo, Vicenza, Italy.
Diagnosis (Berl). 2019 Aug 27;6(3):287-295. doi: 10.1515/dx-2018-0110.
Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.
背景 急性排斥反应（AR）是肾移植（KT）后最常见的并发症之一。科学证据表明，一些位于参与免疫反应以及免疫抑制药物的药代动力学和药效学的基因中的单核苷酸多态性（SNP）与肾移植患者的排斥反应相关。本研究的目的是评估位于六个基因中的一些SNP：白细胞介素-10（IL-10）、肿瘤坏死因子（TNF）、三磷酸腺苷结合盒亚家族B成员1（ABCB1）、尿苷二磷酸葡萄糖醛酸基转移酶家族1成员A9（UGT1A9）、肌苷单磷酸脱氢酶1（IMPDH1）和IMPDH2。方法 我们纳入了KT后至少发生一次AR的病例以及两组对照：KT后未发生任何AR的患者和健康献血者。对DNA进行基因分析。确定杂合性（HET），并对每个SNP进行哈迪-温伯格平衡（HWE）检验。使用QUANTO程序计算样本量，并使用SAS程序（美国北卡罗来纳州卡里市SAS研究所）计算基因关联。结果 在我们之前的初步研究中（病例未达到样本量），结果显示ABCB1基因的SNP rs1045642中的C等位基因和SNP rs2032582中的A等位基因的患者发生AR的频率更高。相比之下，随着样本量的达到，先前数据的趋势未得到证实。结论 我们的研究突出了科学研究中一个普遍被假定的基本方面，即科学研究纳入组的样本量。我们相信我们的研究将在讨论分析的重要性以及达到样本量以评估SNP与所研究事件之间的关联方面为科学界做出重大贡献。
