Department of Family Medicine and Public Health Sciences, The Wayne State University School of Medicine, 3939 Woodward Avenue, Detroit, MI 48201 USA ; Current address: Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, Detroit, MI 48202 USA.
Center for Molecular Medicine and Genetics, The Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201 USA.
Clin Epigenetics. 2015 Apr 21;7(1):47. doi: 10.1186/s13148-015-0080-6. eCollection 2015.
The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race and birth weight. Data was collected on a cohort of 87 live born infants. IGF1 methylation was measured in DNA isolated from the mononuclear fraction of umbilical cord blood collected after delivery. Quantitative, loci-specific methylation was assessed using the Infinium HumanMethylation27 BeadArray (Illumina Inc., San Diego, CA). Locus specific methylation of the IGF1 CpG site was validated on a subset of the original sample (N = 61) using pyrosequencing. Multiple linear regression was used to examine relationships between IGF1 methylation, race, and birth weight. A formal mediation analysis was then used to estimate the relationship of IGF1 methylation to race and birth weight.
Black race was associated with a 7.45% decrease in gestational age-adjusted birth weight (aBW) (P = 0.04) and Black infants had significantly higher IGF1 methylation than non-Black infants (P < 0.05). A one standard deviation increase in IGF1 methylation was associated with a 3.32% decrease in aBW (P = 0.02). Including IGF1 methylation as a covariate, the effect of Black race on aBW was attenuated. A formal mediation analysis showed that the controlled direct effect of Black race on aBW was -6.26% (95% CI = -14.15, 1.06); the total effect of Black race on IGF1 methylation was -8.12% (95% CI = -16.08, -0.55); and the natural indirect effect of Black race on aBW through IGF1 methylation was -1.86% (95% CI = -5.22, 0.18).
The results of the mediation analysis along with the multivariable regression analyses suggest that IGF1 methylation may partially mediate the relationship between Black race and aBW. Such epigenetic differences may be involved in racial disparities observed in perinatal outcomes.
美国黑人新生儿的出生体重一直低于白人新生儿。这种种族间的差异可能与表观遗传差异有关。这些分析的目的是建立 IGF1 甲基化在介导种族与出生体重之间关联的模型。研究数据来自一个 87 例活产婴儿队列。在分娩后采集脐带血单核细胞部分的 DNA 中测量 IGF1 甲基化。使用 Infinium HumanMethylation27 BeadArray（Illumina Inc.，圣地亚哥，CA）评估定量、特定基因座的甲基化。在原始样本的亚组（N=61）上使用焦磷酸测序验证 IGF1 CpG 位点的特定基因座甲基化。使用多元线性回归检验 IGF1 甲基化、种族和出生体重之间的关系。然后使用正式的中介分析来估计 IGF1 甲基化与种族和出生体重的关系。
黑种人种族与胎龄校正出生体重（aBW）降低 7.45%相关（P=0.04），黑人婴儿的 IGF1 甲基化水平明显高于非黑人婴儿（P<0.05）。IGF1 甲基化增加一个标准差与 aBW 降低 3.32%相关（P=0.02）。将 IGF1 甲基化作为协变量包含在内，黑种人种族对 aBW 的影响减弱。正式的中介分析显示，黑种人种族对 aBW 的受控直接效应为-6.26%（95%CI=-14.15，1.06）；黑种人种族对 IGF1 甲基化的总效应为-8.12%（95%CI=-16.08，-0.55）；黑种人种族通过 IGF1 甲基化对 aBW 的自然间接效应为-1.86%（95%CI=-5.22，0.18）。
中介分析以及多变量回归分析的结果表明，IGF1 甲基化可能部分介导了黑种人种族与 aBW 之间的关系。这种表观遗传差异可能与围产期结局中观察到的种族差异有关。
