Barocci S, Ginevri F, Valente U, Torre F, Gusmano R, Nocera A
Department of Immunology, S. Martino Hospital and University of Genoa, Italy.
Transplantation. 1999 Feb 27;67(4):534-8. doi: 10.1097/00007890-199902270-00008.
Despite numerous advances in the areas of organ preservation, histocompatibility, and immunosuppression, chronic deterioration of organ allograft function, referred to as "chronic rejection," still remains the main obstacle to long-term graft survival. The common feature of chronic rejection is a concentric generalized graft arteriosclerosis associated with interstitial fibrosis that reflects an allogeneic injury to graft arteries, possibly worsened by other alloantigen-independent risk factors. The presence of the angiotensin I-converting enzyme (ACE) gene-deleted (D) allele has been associated, when in homozygosity, with increased risk of cardiovascular diseases and with an accelerated progression of organ damage in a variety of kidney diseases. In this study, we analyzed whether the insertion/deletion polymorphism of the ACE gene, because of its negative prognostic impact on cardiovascular and renal pathology, could have any influence on kidney graft survival in pediatric recipients.
DNA was isolated from peripheral blood mononuclear cells from 146 pediatric dialysis patients (mean age: 12.9 years) who received a first kidney graft at our center between December 1985 and July 1997. To rule out any bias due to acute graft losses, only 119 patients who reached a minimum of 12 months of graft survival were considered for statistical analysis. The insertion/deletion polymorphism of the ACE gene was detected using a polymerase chain reaction technique with two flanking primers.
The results demonstrated that (i) the distribution of DD and non-DD (ID + II) genotypes was 36.1% (43 patients) and 63.8% (76 patients), respectively; (ii) actuarial graft survival at 7, 8, 9, and 10 years in patients with non-DD genotype was significantly higher than that in patients with DD genotype (7 years: 94.6% vs. 72.4%, P<0.05; 8 years: 94.6% vs. 62%, P<0.025; 9 years: 87.3% vs. 51.4%, P<0.025; 10 years: 76.3% vs. 25.7%, P<0.01).
In conclusion, the above data indicate that DD genotype is associated in pediatric kidney graft recipients with a shorter long-term kidney graft survival and suggest a possible role of this genotype as a cofactor in the progression of nonimmunological injuries leading to chronic kidney graft failure.
尽管在器官保存、组织相容性和免疫抑制领域取得了众多进展，但器官同种异体移植功能的慢性恶化，即“慢性排斥反应”，仍然是长期移植存活的主要障碍。慢性排斥反应的共同特征是与间质纤维化相关的同心性全身性移植动脉硬化，这反映了对移植动脉的同种异体损伤，可能因其他非同种抗原依赖性风险因素而恶化。血管紧张素I转换酶（ACE）基因缺失（D）等位基因纯合时，与心血管疾病风险增加以及多种肾脏疾病中器官损伤的加速进展有关。在本研究中，我们分析了ACE基因的插入/缺失多态性，由于其对心血管和肾脏病理的负面预后影响，是否会对儿科受者的肾移植存活产生任何影响。
从146名儿科透析患者（平均年龄：12.9岁）的外周血单核细胞中分离DNA，这些患者于1985年12月至1997年7月在我们中心接受了首次肾移植。为排除急性移植丢失导致的任何偏差，仅对119名移植存活至少12个月的患者进行统计分析。使用聚合酶链反应技术和两条侧翼引物检测ACE基因的插入/缺失多态性。
结果表明：（i）DD和非DD（ID + II）基因型的分布分别为36.1%（43例患者）和63.8%（76例患者）；（ii）非DD基因型患者在7、8、9和10年的移植存活精算率显著高于DD基因型患者（7年：94.6%对72.4%，P<0.05；8年：94.6%对62%，P<0.025；9年：87.3%对51.4%，P<0.025；10年：76.3%对25.7%，P<0.01）。
总之，上述数据表明，在儿科肾移植受者中，DD基因型与长期肾移植存活时间较短有关，并表明该基因型可能作为导致慢性肾移植失败的非免疫性损伤进展中的一个辅助因素发挥作用。
