Center for Health Outcomes and Prevention Research, Sanford Research, Sioux Falls, SD, USA.
BMC Pediatr. 2012 Mar 20;12:33. doi: 10.1186/1471-2431-12-33.
While a possible link between assisted reproductive technology (ART) and rare imprinting disorders has been found, it is not clear if this is indicative of subtler disruptions of epigenetic mechanisms. Results from previous studies have been mixed, but some methylation differences have been observed.
Children conceived through ART and children conceived spontaneously were recruited for this cross-sectional study. Information about reproductive history, demographic factors, birth characteristics, and infertility treatment was obtained from maternal interview and medical records. Peripheral blood lymphocytes and buccal cell samples were collected from participating children. Methylation analysis was performed on five loci using pyrosequencing. Statistical analysis of methylation differences was performed using linear regression with generalized estimating equations. Results are reported as differences with 95% confidence intervals (CI).
A total of 67 ART children and 31 spontaneously conceived (SC) children participated. No significant difference in methylation in lymphocyte samples was observed between groups for any loci. Possible differences were found in buccal cell samples for IGF2 DMR0 (Difference: 2.07; 95% confidence interval (CI): -0.28, 4.42; p = 0.08) and IGF2R (Difference: -2.79; 95% CI: -5.74, 0.16; p = 0.06). Subgroup analysis indicated potential lower methylation in those whose parents used ART for unexplained infertility.
Observed differences in methylation between the ART and SC groups were small for all loci in the two sample types examined and no statistical differences were observed. It is still unclear whether or not small differences observed in several studies represent a real difference between groups and if this difference is biologically meaningful. Larger studies with long term follow-up are needed to fully answer these questions.
虽然已经发现辅助生殖技术（ART）与罕见印记疾病之间可能存在联系，但目前尚不清楚这是否表明表观遗传机制受到更细微的干扰。先前的研究结果参差不齐，但已经观察到一些甲基化差异。
本横断面研究招募了通过 ART 受孕的儿童和自然受孕的儿童。通过对母亲的访谈和医疗记录，获得了有关生殖史、人口统计学因素、出生特征和不孕治疗的信息。从参与的儿童中采集外周血淋巴细胞和口腔细胞样本。使用焦磷酸测序法对五个基因座进行甲基化分析。使用广义估计方程的线性回归进行甲基化差异的统计分析。结果以差异和 95%置信区间（CI）报告。
共有 67 名 ART 儿童和 31 名自然受孕（SC）儿童参与。两组间在任何基因座的淋巴细胞样本中均未观察到甲基化差异。在口腔细胞样本中，IGF2 DMR0（差异：2.07；95%置信区间（CI）：-0.28，4.42；p=0.08）和 IGF2R（差异：-2.79；95% CI：-5.74，0.16；p=0.06）可能存在差异。亚组分析表明，对于父母因不明原因不孕而使用 ART 的个体，其甲基化水平可能较低。
在两种样本类型中，在所有基因座上观察到的 ART 和 SC 组之间的甲基化差异均较小，且未观察到统计学差异。目前尚不清楚在几个研究中观察到的微小差异是否代表组间的真实差异，以及这种差异是否具有生物学意义。需要进行更大规模、长期随访的研究，以充分回答这些问题。
