Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
BMC Med. 2010 Dec 21;8:87. doi: 10.1186/1741-7015-8-87.
Despite evidence linking obesity to impaired immune function, little is known about the specific mechanisms. Because of emerging evidence that immune responses are epigenetically regulated, we hypothesized that DNA methylation changes are involved in obesity induced immune dysfunction and aimed to identify these changes.
We conducted a genome wide methylation analysis on seven obese cases and seven lean controls aged 14 to 18 years from extreme ends of the obesity distribution and performed further validation of six CpG sites from six genes in 46 obese cases and 46 lean controls aged 14 to 30 years.
In comparison with the lean controls, we observed one CpG site in the UBASH3A gene showing higher methylation levels and one CpG site in the TRIM3 gene showing lower methylation levels in the obese cases in both the genome wide step (P = 5 × 10(-6) and P = 2 × 10(-5) for the UBASH3A and the TRIM3 gene respectively) and the validation step (P = 0.008 and P = 0.001 for the UBASH3A and the TRIM3 gene respectively).
Our results provide evidence that obesity is associated with methylation changes in blood leukocyte DNA. Further studies are warranted to determine the causal direction of this relationship as well as whether such methylation changes can lead to immune dysfunction.
尽管有证据表明肥胖与免疫功能受损有关，但对于具体的机制知之甚少。由于有新的证据表明免疫反应受到表观遗传调控，我们假设 DNA 甲基化变化与肥胖引起的免疫功能障碍有关，并旨在确定这些变化。
我们对来自肥胖分布两端的 7 名 14 至 18 岁的肥胖病例和 7 名瘦对照者进行了全基因组甲基化分析，并对来自 14 至 30 岁的 46 名肥胖病例和 46 名瘦对照者的 6 个基因中的 6 个 CpG 位点进行了进一步验证。
与瘦对照组相比，我们在全基因组分析步骤中观察到 UBASH3A 基因中的一个 CpG 位点显示出较高的甲基化水平，而在 TRIM3 基因中的一个 CpG 位点显示出较低的甲基化水平，肥胖病例与瘦对照组相比（UBASH3A 和 TRIM3 基因的 P 值分别为 5×10(-6)和 2×10(-5)），验证步骤中也观察到了相同的结果（UBASH3A 和 TRIM3 基因的 P 值分别为 0.008 和 0.001）。
我们的研究结果提供了证据，表明肥胖与血液白细胞 DNA 中的甲基化变化有关。需要进一步的研究来确定这种关系的因果方向，以及这种甲基化变化是否会导致免疫功能障碍。
