Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12.
Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12.
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DOI：
10.1371/journal.pone.0033290
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Relton CL
中科院分区：
文献类型：
--
作者：
McKay JA;Groom A;Potter C;Coneyworth LJ;Ford D;Mathers JC;Relton CL
出生时DNA甲基化模式的个体间差异可以通过环境、遗传和随机因素的影响来解释。本研究探讨了人类婴儿DNA甲基化变异的遗传和非遗传决定因素。鉴于其在提供甲基DNA甲基化中的核心作用，本研究侧重于叶酸代谢方面。通过焦磷酸测序®对430例婴儿的DNA甲基化进行了全局（LUMA）和基因特异性（IGF2, ZNT5, IGFBP3）的量化。在婴儿和母亲的DNA中分析了6个与叶酸吸收和代谢有关的基因（MTHFR、MTRR、FOLH1、c - β s、RFC1、SHMT）的7个多态性。测定红细胞叶酸和血清维生素B12浓度作为维生素状态的指标。DNA甲基化模式与性别、妊娠期长短、母婴红细胞叶酸、母婴血清维生素B12、母亲年龄、吸烟和基因型等协变量之间的关系进行了测试。妊娠期长短与IGF2甲基化呈正相关（rho = 0.11, p = 0.032），与ZNT5甲基化呈负相关（rho = - 0.13, p = 0.017）。IGFBP3位点的甲基化与婴儿维生素B12浓度呈负相关（rho = - 0.16, p = 0.007），而DNA甲基化与母体维生素B12浓度呈负相关（rho = 0.18, p = 0.044）。对叶酸通路基因常见遗传变异的分析显示，婴儿MTRR 66G>A基因型与DNA甲基化相关（χ2 = 8.82, p = 0.003），母亲MTHFR 677C>T基因型与IGF2甲基化相关（χ2 = 2.77, p = 0.006）。这些数据支持了一种假设，即环境和遗传因素都参与了单碳代谢，影响婴儿的DNA甲基化。具体来说，研究结果强调了维生素B12状态、婴儿MTRR基因型和母亲MTHFR基因型的重要性，所有这些都可能影响DNA甲基化甲基群的供应。此外，妊娠期长度似乎是婴儿DNA甲基化模式的重要决定因素。
Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA) and gene specific (IGF2, ZNT5, IGFBP3) DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT) involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032) and inversely with ZNT5 methylation (rho = −0.13, p = 0.017). Methylation of the IGFBP3 locus correlated inversely with infant vitamin B12 concentration (rho = −0.16, p = 0.007), whilst global DNA methylation correlated inversely with maternal vitamin B12 concentrations (rho = 0.18, p = 0.044). Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ2 = 8.82, p = 0.003) and maternal MTHFR 677C>T genotype with IGF2 methylation (χ2 = 2.77, p = 0.006). These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for DNA methylation. In addition, gestational length appears to be an important determinant of infant DNA methylation patterns.
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影响因子：
3.7
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
通讯作者：
Ophoff RA
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
3.7
作者：
Guerrero-Preston, Rafael;Goldman, Lynn R.;Sidransky, David
通讯作者：
Sidransky, David
影响因子：
4
作者：
Chase, DS;Tawn, EJ;Burn, J
通讯作者：
Burn, J
影响因子：
3.5
作者：
Heijmans, Bastiaan T.;Kremer, Dennis;Slagboom, P. Eline
通讯作者：
Slagboom, P. Eline