Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation, and child autistic traits: The moderating role of OXTR rs53576 genotype.
Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation, and child autistic traits: The moderating role of OXTR rs53576 genotype.
复制标题
DOI：
10.1002/aur.1681
复制
发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Bakermans-Kranenburg MJ
中科院分区：
文献类型：
--
作者：
Rijlaarsdam J;van IJzendoorn MH;Verhulst FC;Jaddoe VW;Felix JF;Tiemeier H;Bakermans-Kranenburg MJ
编码催产素受体（OXTR）的基因位于染色体3 p25上，被认为是解释自闭症遗传易感性的一个有希望的候选者。尽管有几条证据表明OXTR SNP rs 53576（G/A）变异与社会行为有关，但研究结果并不一致，可能是因为压力暴露后的DNA甲基化被排除在外。本研究探讨了OXTR rs 53576基因型、压力暴露和OXTR甲基化对儿童自闭症特征的主要影响和交互作用。产前母亲的压力暴露，而不是OXTR rs 53576基因型和OXTR甲基化，对儿童自闭症特征的主要影响。对于一般的儿童自闭症特征和特别是社会沟通问题，我们观察到一个显着的OXTR rs 53576基因型通过OXTR甲基化相互作用。更具体地说，OXTR甲基化水平与OXTR rs 53576 G等位基因纯合子儿童的社会问题呈正相关，但与A等位基因携带者无关。这些结果强调了整合表位等位基因信息的重要性，并支持OXTR甲基化在儿童自闭症特征中的作用。研究OXTR SNP rs 53576（G-A）在社会行为中变异的研究结果不一致，可能是因为压力暴露后的DNA甲基化被排除在外。我们的目标是检查新生儿OXTR DNA甲基化的OXTR rs 53576等位基因特异性敏感性，其与（1）产前母体压力复合物和（2）儿童自闭症特征有关。在参与R世代研究的总共743名儿童中收集了从胎儿生命到6岁的前瞻性数据。产前母亲压力暴露与儿童自闭症特征独特相关，但与OXTR rs 53576 G等位基因纯合儿童和A等位基因携带者的OXTR甲基化无关。对于一般的儿童自闭症特征和特别是社会沟通问题，我们观察到一个显着的OXTR rs 53576基因型通过OXTR甲基化相互作用的情况下的主要影响，这表明相反的影响相互抵消。事实上，OXTR甲基化水平与OXTR rs 53576 G等位基因纯合子儿童的社会问题呈正相关，但与A等位基因携带者无关。这些结果强调了整合表位等位基因信息的重要性，并支持OXTR甲基化在儿童自闭症特征中的作用。
The gene encoding the oxytocin receptor (OXTR), localized on chromosome 3p25, is considered a promising candidate for explaining genetic vulnerability to autistic traits. Although several lines of evidence implicate OXTR SNP rs53576 (G/A) variation in social behavior, findings have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. This study investigated the main and interactive effects of OXTR rs53576 genotype, stress exposure, and OXTR methylation on child autistic traits. Prenatal maternal stress exposure, but not OXTR rs53576 genotype and OXTR methylation, showed a main effect on child autistic traits. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction. More specifically, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits. Findings of studies investigating OXTR SNP rs53576 (G-A) variation in social behavior have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. Our goal was to examine OXTR rs53576 allele-specific sensitivity for neonatal OXTR DNA methylation in relation to (1) a prenatal maternal stress composite, and (2) child autistic traits. Prospective data from fetal life to age 6 years were collected in a total of 743 children participating in the Generation R Study. Prenatal maternal stress exposure was uniquely associated with child autistic traits but was unrelated to OXTR methylation across both OXTR rs53576 G-allele homozygous children and A-allele carriers. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction in the absence of main effects, suggesting that opposing effects cancelled each other out. Indeed, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits.