Snyder Laurie D, Hartwig Matthew G, Ganous Tonya, Davis R Duane, Herczyk Walter F, Reinsmoen Nancy L, Schwartz David A, Palmer Scott M
Division of Pulmonary, Allergy and Critical Care, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Heart Lung Transplant. 2006 Nov;25(11):1330-5. doi: 10.1016/j.healun.2006.07.001. Epub 2006 Oct 12.
Cytokine polymorphisms are inconsistently associated with transplant rejection and other adverse outcomes. To address this controversy, we evaluated cytokine single nucleotide polymorphisms (SNPs) in a lung transplant cohort.
All patients who underwent lung transplantation from 1993 to 1998 and had post-transplant survival of at least 6 months were included in the initial analysis. Subjects were genotyped for: TNF-alpha -308 G/A; IFN-gamma +874 A/T; TGF-beta1 +869 T/C and +915 G/C; IL-10 -1082 A/G, -819 C/T and -592 C/A; and IL-6 -174 G/C. End-points were onset of broncholitis obliterans syndrome (BOS) and survival.
In the cohort, 78 subjects, with an overall mean +/- SE survival 2,339 +/- 117 days, had no correlation between onset of BOS1, BOS2 or survival with TNF-alpha, IFN-gamma, TGF-beta1 or IL-10 gene polymorphisms. However, IL-6 polymorphisms GG or GC were associated with an earlier onset of BOS1 (p = 0.039), BOS2 (p = 0.021), and decreased overall post-transplant survival (p = 0.038). A second cohort of more recent lung transplant recipients did not validate an association between IL-6 polymorphisms and earlier onset of BOS1 (p = 0.70), BOS2 (p = 0.54) or overall post-transplant survival (p = 0.25).
Polymorphisms of TNF-alpha, IFN-gamma, TGF-beta1, IL-10 and IL-6 do not appear to influence the onset of BOS or graft survival in recipients.
细胞因子多态性与移植排斥及其他不良后果之间的关联并不一致。为解决这一争议,我们在一个肺移植队列中评估了细胞因子单核苷酸多态性(SNP)。
初始分析纳入了1993年至1998年间接受肺移植且移植后存活至少6个月的所有患者。对受试者进行基因分型检测:肿瘤坏死因子-α(TNF-α)-308 G/A;干扰素-γ(IFN-γ)+874 A/T;转化生长因子-β1(TGF-β1)+869 T/C和+915 G/C;白细胞介素-10(IL-10)-1082 A/G、-819 C/T和-592 C/A;以及白细胞介素-6(IL-6)-174 G/C。观察终点为闭塞性细支气管炎综合征(BOS)的发病情况和生存率。
在该队列中,78名受试者的总体平均±标准误生存时间为2339±117天,BOS1、BOS2的发病情况或生存率与TNF-α、IFN-γ、TGF-β1或IL-10基因多态性之间无相关性。然而,IL-6基因多态性GG或GC与BOS1(p = 0.039)、BOS2(p = 0.021)的较早发病以及移植后总体生存率降低(p = 0.038)相关。另一组近期肺移植受者未证实IL-6基因多态性与BOS1(p = 0.70)、BOS2(p = 0.54)的较早发病或移植后总体生存率(p = 0.25)之间存在关联。
TNF-α、IFN-γ、TGF-β1、IL-10和IL-6的多态性似乎不影响受者BOS的发病或移植物存活。