Department of Paediatrics, Glostrup Hospital and University of Copenhagen, Denmark.
Diabet Med. 2012 Jun;29(6):734-41. doi: 10.1111/j.1464-5491.2011.03544.x.
The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes.
Two hundred and twenty-seven patients from the Hvidoere Study Group were classified in four different progression groups as assessed by change in stimulated C-peptide from 1 to 6 months. CA repeat variants of the IL-10 and IFNγ gene were genotyped and serum levels of IL-10 and IFNγ were measured at 1, 6 and 12 months.
IL-10 decreased (P < 0.001) by 7.7% (1 month), 10.4% (6 months) and 8.6% (12 months) per year increase in age of child, while a twofold higher C-peptide concentration at 1 month (p = 0.06), 6 months (P = 0.0003) and 12 months (P = 0.02) was associated with 9.7%, 18.6% and 9.7% lower IL-10 levels, independent of each other. IL-10 concentrations did not associate with the disease progression groups. By contrast, IFNγ concentrations differed between the four progression groups at 6 and 12 months (P = 0.02 and P = 0.01, respectively); patients with rapid progressing disease had the highest levels at both time points. Distribution of IL-10 and IFNγ genotypes was equal among patients from the progression groups.
IL-10 serum levels associate inversely with age and C-peptide. As age and C-peptide also associate, a triangular association is proposed. Genetic influence on IL-10 production seems to be masked by distinct disease mechanisms. Increased serum IFNγ concentrations associate with rapid disease progression. Functional genetic variants do not associate with a single progression pattern group, implying that disease processes override genetically predisposed cytokine production.
本研究旨在探讨新诊断为 1 型糖尿病的儿科患者疾病进展与年龄、血清白细胞介素 10（IL-10）和干扰素 γ（IFNγ）的关系及其遗传相关性。
Hvidoere 研究组的 227 例患者根据 1 至 6 个月刺激 C 肽的变化分为四个不同的进展组。对 IL-10 和 IFNγ 基因的 CA 重复变异进行基因分型，并在 1、6 和 12 个月时测量血清 IL-10 和 IFNγ 水平。
儿童年龄每增加 1 岁，IL-10 水平分别降低 7.7%（1 个月）、10.4%（6 个月）和 8.6%（12 个月）（P < 0.001），而 1 个月（p = 0.06）、6 个月（P = 0.0003）和 12 个月（P = 0.02）时 C 肽浓度增加两倍与 IL-10 水平降低 9.7%、18.6%和 9.7%独立相关。IL-10 浓度与疾病进展组之间没有相关性。相比之下，IFNγ 浓度在 6 个月和 12 个月时在四个进展组之间存在差异（P = 0.02 和 P = 0.01）；疾病进展较快的患者在这两个时间点的水平最高。IL-10 和 IFNγ 基因型在进展组患者中的分布相同。
IL-10 血清水平与年龄和 C 肽呈负相关。由于年龄和 C 肽也相关，因此提出了一个三角形的关联。遗传对 IL-10 产生的影响似乎被不同的疾病机制所掩盖。血清 IFNγ 浓度升高与疾病快速进展相关。功能遗传变异与单一进展模式组无关，这意味着疾病过程超过了遗传易感性细胞因子的产生。
