Wehkalampi Karoliina, Muurinen Mari, Wirta Sara Bruce, Hannula-Jouppi Katariina, Hovi Petteri, Järvenpää Anna-Liisa, Eriksson Johan G, Andersson Sture, Kere Juha, Kajantie Eero
Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland ; Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
PLoS One. 2013 Jun 19;8(6):e67379. doi: 10.1371/journal.pone.0067379. Print 2013.
People born preterm at very low birth weight (VLBW, ≤1500g) have higher rates of risk factors for adult-onset diseases, including cardiovascular diseases and type 2 diabetes. These risks may be mediated through epigenetic modification of genes that are critical to normal growth and development.
We measured the methylation level of an imprinted insulin-like-growth-factor 2 (IGF2) locus (IGF2/H19) in young adults born preterm at VLBW and in their peers born at term. We studied 158 VLBW and 161 control subjects aged 18 to 27 years from the Helsinki Study of Very Low Birth Weight Adults. Methylation fraction at two IGF2 differentially methylated regions (DMRs) - IGF2 antisense transcript (IGF2AS, also known as IGF2 DMR0) and last exon of IGF2 (IGF2_05, also known as IGF2 DMR2) - were measured with Sequenom Epityper. We used linear regression and adjustment for covariates to compare methylation fractions at these DMRs between VLBW and control subjects.
At one IGF2AS CpG site, methylation was significantly lower in VLBW than in control subjects, mean difference -0.017 (95% CI; -0.028, -0.005), P = 0.004. Methylation at IGF2_05 was not different between the groups.
Methylation of IGF2AS is altered 20 years after preterm birth at VLBW. Altered methylation may be a mechanism of later increased disease risk but more data are needed to indicate causality.
极低出生体重（VLBW，≤1500g）的早产儿患成人期疾病风险因素的几率更高，包括心血管疾病和2型糖尿病。这些风险可能通过对正常生长发育至关重要的基因的表观遗传修饰来介导。
我们测量了极低出生体重早产儿及足月儿的印记胰岛素样生长因子2（IGF2）基因座（IGF2/H19）的甲基化水平。我们研究了来自赫尔辛基极低出生体重成人研究的158名极低出生体重者和161名年龄在18至27岁的对照受试者。使用Sequenom Epityper测量了两个IGF2差异甲基化区域（DMR）——IGF2反义转录本（IGF2AS，也称为IGF2 DMR0）和IGF2的最后一个外显子（IGF2_05，也称为IGF2 DMR2）的甲基化分数。我们使用线性回归并对协变量进行调整，以比较极低出生体重者和对照受试者在这些DMR处的甲基化分数。
在一个IGF2AS CpG位点，极低出生体重者的甲基化水平显著低于对照受试者，平均差异为-0.017（95%CI：-0.028，-0.005），P = 0.004。两组之间IGF2_05的甲基化无差异。
极低出生体重早产20年后，IGF2AS的甲基化发生改变。甲基化改变可能是后期疾病风险增加的一种机制，但需要更多数据来表明因果关系。
