College of Pharmacy, Seoul National University, Seoul, Korea.
Clin Ther. 2012 Feb;34(2):295-304. doi: 10.1016/j.clinthera.2012.01.010. Epub 2012 Feb 1.
The interleukin-6 (IL-6) -174 G>C genetic polymorphism has been implicated to play an important role in acute graft-versus-host disease (aGVHD). However, previous studies have yielded inconclusive results as to its role in patient susceptibility to aGVHD, and no study to date has systematically analyzed this polymorphism.
A meta-analysis of the published evidence was conducted to estimate the true effect of the IL-6 -174 G>C genetic polymorphism in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients and donors on the risk of aGVHD.
Seven cohort studies, comprising 1287 recipient and donor pairs, were included after eliminating 62 studies that met the following exclusion criteria: irrelevant studies other than cohort studies, without sufficient data, and with overlapping data. Although interstudy heterogeneity existed, most studies were conducted in the United States or Europe and included adult patients with hematologic disease who received alloHSCT from human leukocyte antigen-matched or identical sibling donors. The effect of the polymorphism on aGVHD risk (grades I-IV, II-IV, and III-IV) was estimated from odds ratios with 95% confidence intervals for the dominant genetic model and recessive model, respectively.
Patients who received grafts from donors with the IL-6 G allele experienced more frequent grade I-IV aGVHD (odds ratio = 3.304 [95% confidence interval, 1.456-7.494]) and grade II-IV aGVHD (odds ratio = 1.738 [95% CI, 1.006 - 3.001]).
To our knowledge, this is the first meta-analysis to evaluate the relation between a non-human leukocyte antigen gene polymorphism and the risk of aGVHD. Our meta-analysis combined the results of several studies and demonstrated that the donor IL-6 G allele is associated with an increased risk of grades I-IV and II-IV aGVHD.
白细胞介素 6（IL-6）-174G>C 基因多态性被认为在急性移植物抗宿主病（aGVHD）中起重要作用。然而，先前的研究对于其在患者发生 aGVHD 易感性中的作用得出的结论并不一致，迄今为止尚无研究系统地分析这种多态性。
对已发表的证据进行荟萃分析，以评估 IL-6-174G>C 基因多态性在异基因造血干细胞移植（alloHSCT）患者和供者中对 aGVHD 风险的真实影响。
在排除了 62 项不符合以下排除标准的研究后，纳入了 7 项队列研究，共包括 1287 对受者和供者：与队列研究无关的研究、没有足够数据的研究以及数据重叠的研究。尽管存在研究间异质性，但大多数研究在美国或欧洲进行，包括接受来自人类白细胞抗原匹配或同卵兄弟姐妹供者的 alloHSCT 的血液系统疾病成年患者。采用优势遗传模型和隐性遗传模型，分别用比值比及其 95%置信区间来估计该多态性对 aGVHD 风险（I-IV 级、II-IV 级和 III-IV 级）的影响。
接受 IL-6 G 等位基因供体移植物的患者发生 I-IV 级 aGVHD 的频率更高（比值比=3.304[95%置信区间，1.456-7.494]）和 II-IV 级 aGVHD（比值比=1.738[95%CI，1.006-3.001]）。
据我们所知，这是第一项评估非人类白细胞抗原基因多态性与 aGVHD 风险之间关系的荟萃分析。我们的荟萃分析综合了几项研究的结果，表明供体 IL-6 G 等位基因与 I-IV 级和 II-IV 级 aGVHD 的风险增加相关。
