Artifoni Lina, Benetti Elisa, Centi Sonia, Negrisolo Susanna, Ghiggeri Gian Marco, Ginevri Fabrizio, Ghio Luciana, Edefonti Alberto, Brambilla Caterina, Cagni Nicoletta, Murer Luisa
Department of Paediatrics, University of Padua, Italy.
Nephrol Dial Transplant. 2009 Sep;24(9):2931-7. doi: 10.1093/ndt/gfp161. Epub 2009 Apr 6.
The main cause of reduced long-term graft survival is chronic allograft injury. Cardiovascular risk factors such as hyperhomocysteinaemia, accumulation of asymmetric dimethylarginine, increased oxidative stress and decreased production of nitric oxide seem to play an important role. Functional polymorphisms of the endothelial isoform of nitric oxide synthase (NOS) gene cause an alteration in nitric oxide production. Nitric oxide levels, and thus oxidative stress, are also influenced by hyperhomocysteinaemia.
We carried out a genetic analysis of endothelial nitric oxide synthase (eNOS) 894G>T, methionine synthase (MTR) 2756A>G and methylenetetrahydrofolate reductase (MTHFR) 677C>T/1298A>C in 268 renal allograft recipient/donor (D/R) matches, with respect to long-term graft survival.
While MTHFR 677C>T/1298A>G and MTR 2756A>G polymorphism distribution in both recipients (R) and donors (D) showed no significant difference between matches with loss of graft function and those with long-term graft survival, the frequency of the eNOS 894TT genotype of donors was significantly increased (P = 0.040) in matches with better graft survival. The multivariate analysis identified the eNOS 894 genotype and clinically acute rejection episodes as independent risk factors for graft loss (P = 0.0406 and P = 0.0093, respectively).
The association between eNOS 894G>T polymorphism of donors and graft survival seems to suggest a role for this gene in chronic allograft injury; however, further studies are needed to confirm this hypothesis.
长期移植物存活降低的主要原因是慢性移植物损伤。心血管危险因素，如高同型半胱氨酸血症、不对称二甲基精氨酸的蓄积、氧化应激增加和一氧化氮生成减少，似乎起着重要作用。一氧化氮合酶（NOS）基因内皮型的功能多态性导致一氧化氮生成改变。一氧化氮水平，进而氧化应激，也受高同型半胱氨酸血症影响。
我们对268例肾移植受者/供者（D/R）配对样本进行了内皮型一氧化氮合酶（eNOS）894G>T、甲硫氨酸合成酶（MTR）2756A>G和亚甲基四氢叶酸还原酶（MTHFR）677C>T/1298A>C的基因分析，以研究长期移植物存活情况。
虽然MTHFR 677C>T/1298A>G和MTR 2756A>G多态性在移植物功能丧失的配对组和长期移植物存活的配对组的受者（R）和供者（D）中的分布无显著差异，但在移植物存活较好的配对组中，供者的eNOS 894TT基因型频率显著增加（P = 0.040）。多变量分析确定eNOS 894基因型和临床急性排斥反应发作是移植物丢失的独立危险因素（分别为P = 0.0406和P = 0.0093）。
供者eNOS 894G>T多态性与移植物存活之间的关联似乎表明该基因在慢性移植物损伤中起作用；然而，需要进一步研究来证实这一假说。
