Polymorphisms in the maternal sex steroid pathway are associated with behavior problems in male offspring.
Polymorphisms in the maternal sex steroid pathway are associated with behavior problems in male offspring.
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DOI：
10.1097/ypg.0b013e328351850b
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发表时间：
2012-06
影响因子：
0.9
通讯作者：
Wolff MS
中科院分区：
文献类型：
--
作者：
Miodovnik A;Diplas AI;Chen J;Zhu C;Engel SM;Wolff MS
母体性类固醇产生和代谢的轻微干扰可能会干扰正常的胎儿神经发育。母体雌激素和雄激素的平衡可能对胎儿有直接影响，可能影响胎儿下丘脑-垂体-性腺轴或可能改变胎儿大脑内的局部激素活性。我们研究了 CYP17、CYP19 和 CYP1B1 的母体功能多态性，它们控制性类固醇生物合成和代谢中的三个主要酶步骤，与儿童行为相关。西奈山儿童环境健康研究招募了 1998 年至 2002 年的多种族城市怀孕队列 (n = 404)。 DNA 是从母血 (n=149) 和新生儿脐带血 (n=53) 中获得的。每次访问时，母亲们都会填写儿童行为评估系统（BASC），这是一份由家长报告的调查问卷，用于评估儿童的行为问题。我们关注与多动症更常见的问题行为（多动症、注意力问题、外化行为、品行障碍、适应性差），以观察性类固醇产生和代谢中的母体遗传变异是否影响后代的两性行为。与女性后代相比，更活跃的基因变异与男性后代的注意力问题和较差的适应技能显着相关。 CYP19 变异等位基因还与男孩在多动、外化问题综合和适应性技能综合量表上的较差分数显着相关（p < 0.05）。我们观察到携带性类固醇途径功能多态性的母亲的雄性后代的适应不良行为。最强的关联是在注意力缺陷多动障碍常受影响的领域。
Slight perturbations in maternal sex steroid production and metabolism may interfere with normal fetal neurodevelopment. The balance of maternal estrogens and androgens may have direct fetal effects, may influence the fetal hypothalamic-pituitary-gonadal axis or may alter local hormonal activity within the fetal brain. We investigated maternal functional polymorphisms of CYP17, CYP19 and CYP1B1, which control three major enzymatic steps in sex steroid biosynthesis and metabolism, in relation to childhood behaviors. The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic urban pregnancy cohort from 1998–2002 (n = 404). DNA was obtained from maternal blood (n=149) and from neonatal cord blood (n=53). At each visit, mothers completed the Behavior Assessment System for Children (BASC), a parent-reported questionnaire used to evaluate children for behavior problems. We focused on problem behaviors more commonly associated with ADHD (hyperactivity, attention problems, externalizing behaviors, conduct disorder, poor adaptability) to see if maternal genetic variants in sex steroid production and metabolism influence sexually-dimorphic behaviors in offspring. The more active gene variants were significantly associated with Attention Problems and poorer Adaptive Skills in male compared to female offspring. The CYP19 variant allele was also significantly associated with worse scores for boys on the Hyperactivity, Externalizing Problems Composite and Adaptive Skills Composite scales (p < 0.05). We observed maladaptive behaviors in the male offspring of mothers who carried functional polymorphisms in the sex steroid pathway. The strongest associations were in domains commonly affected in Attention Deficit-Hyperactivity Disorder.