Interleukin-6 polymorphism: A genetic risk factor for cardiac transplant related coronary vasculopathy?
Interleukin-6 polymorphism: A genetic risk factor for cardiac transplant related coronary vasculopathy?
复制标题
DOI：
10.1016/j.healun.2004.03.016
复制
发表时间：
2005-05-01
影响因子：
8.9
通讯作者：
Brooks, NH
中科院分区：
文献类型：
--
作者：
Densem, CG;Ray, M;Brooks, NH
目的：白介素-(IL-) 6 是一种多效细胞因子，对急性期反应、炎症和血管功能有影响。 IL-6 基因启动子区第 174 位存在 G 至 C 多态性。我们研究了这种多态性对心脏移植相关冠状动脉血管病变 (CV) 发展的影响。方法：序列特异性聚合酶链反应鉴定了 116 名心脏移植受者的 -174*G/C 等位基因。通过移植后冠状动脉造影的常规监测来鉴定冠状动脉疾病。结果：移植组和对照组之间 - 174*G/C 多态性的患病率不同； *CC 27.6%、*CG 45.7% 和 *GG 26.7% 分别对比 13.2%、44.1% 和 42.7% (P = 0.004)。首次诊断 CV 的中位时间在 3 个等位基因之间不同； *CC 2.8 年（2.0-4.0）； *CG 3.9 年 (2.1-4-5)； *GG 5.3 年 (3.2-6.1) (1) = 0.05)。根据 Kaplan-Meier 生存分析，C 纯合子明显早于其他群体 (1) = 0.035) 发生 CV。 5 年时，100% 的 C 纯合子有 CV 证据。 G 纯合子的 CV 发病更为缓慢，5 岁时患病率约为 60%。 *CC 基因型是 CV 发展最具预测性的危险因素（风险比 4.2 (95% CI 1.3-12.9)；p = 0.014）。供体年龄的增加也很显着（风险比 1.04（95% CI，1.0-1.08）；p = 0.023）。结论：IL-6 基因启动子区域内第 174 位的多态性可能是心脏移植相关冠状动脉血管病变的重要危险因素。这可以改善患者选择并允许量身定制的免疫抑制治疗。心肺移植杂志 2005 年；24：559-65。国际心肺移植协会版权所有 (c) 2005。
Aims: Interleukin-(IL-) 6 is a pleiotropic cytokine with effects on the acute phase response, inflammation, and vascular function. A G to C polymorphism has been described at position - 174 in the promoter region of the IL-6 gene. We investigated the influence of this polymorphism on the development of cardiac transplant related coronary vasculopathy (CV).Methods: Sequence specific polymerase chain reaction identified the -174*G/C allele for 116 cardiac transplant recipients. Coronary disease was identified by routine surveillance post-transplant coronary angiography.Results: Prevalence of the - 174*G/C polymorphism was different between the transplant and control cohorts; *CC 27.6%, *CG 45.7%, and *GG 26.7% vs. 13.2%, 44.1% and 42.7% respectively (P = 0.004). Median time to the first diagnosis of CV was different between the 3 alleles; *CC 2.8 years (2.0-4.0); *CG 3.9 years (2.1-4-5); *GG 5.3 years (3.2-6.1) (1) = 0.05). By Kaplan-Meier survival analysis C homozygotes developed CV significantly earlier than the other cohorts (1) = 0.035). At 5 years 100% of C homozygotes had evidence for CV. G homozygotes had a more gradual onset of CV with an approximate 60% prevalence at 5 years. *CC genotype was the most predictive risk factor for CV development (Hazard ratio 4.2 (95% CI 1.3-12.9); p = 0.014). Increasing donor age was also significant (Hazard ratio 1.04 (95% CI, 1.0-1.08); p = 0.023).Conclusions: Polymorphism at position - 174 within the promoter region of the IL-6 gene may be an important risk factor for cardiac transplant related coronary vasculopathy. This may improve patient selection and allow tailored immunosuppressive treatment. J Heart Lung Transplant 2005;24:559-65. Copyright (c) 2005 by the International Society for Heart and Lung Transplantation.