Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism.
Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism.
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DOI：
10.1097/ede.0b013e31821d0e30
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发表时间：
2011-07
期刊：
影响因子：
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通讯作者：
Hertz-Picciotto I
中科院分区：
文献类型：
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作者：
Schmidt RJ;Hansen RL;Hartiala J;Allayee H;Schmidt LC;Tancredi DJ;Tassone F;Hertz-Picciotto I
自闭症的病因尚不清楚。与母体营养因子的关联及其与基因变异的相互作用尚未报道。2003-2009年，北加州家庭被纳入了基于人群的CHARGE（遗传和环境的儿童自闭症风险）病例对照研究。在加州大学戴维斯分校神经发育障碍医学调查研究所，使用标准化的临床评估对24-60个月的儿童进行评估，并确认患有自闭症（n = 288）、自闭症谱系障碍（n = 141）或典型发育（n = 278）。我们计算了自闭症与回顾性收集孕妇孕前和孕期维生素摄入量之间关系的校正比值比（ORs）。我们探索了与母亲或孩子携带的单碳代谢（MTHFR， COMT， MTRR， BHMT, FOLR2， CBS和TCN2）相关的功能遗传变异的相互作用效应。自闭症儿童的母亲在怀孕前三个月或怀孕第一个月服用产前维生素的可能性低于正常发育儿童的母亲（or = 0.62[95%可信区间= 0.42-0.93]）。在母体MTHFR 677 TT、CBS rs234715 GT+TT和儿童COMT 472 AA基因型中观察到显著的相互作用效应，当母亲未报告妊娠期服用产前维生素时，患自闭症的风险更高（分别为4.5[1.4-14.6]、2.6[1.2-5.4]和7.2[2.3-22.4]）。如果母亲有其他单碳代谢途径基因变异，并且产前没有摄入维生素，那么孩子的风险也更大。孕产期服用产前维生素可以降低孩子患自闭症的风险，尤其是对基因易感的母亲和孩子。复制和机械研究是必要的。
Causes of autism are unknown. Associations with maternal nutritional factors and their interactions with gene variants have not been reported. Northern California families were enrolled from 2003–2009 in the CHARGE (CHildhood Autism Risks from Genetics and Environment) population-based case-control study. Children aged 24–60 months were evaluated and confirmed to have autism (n = 288), autism spectrum disorder (n = 141), or typical development (n = 278) at the University of California–Davis Medical Investigation of Neurodevelopmental Disorders Institute using standardized clinical assessments. We calculated adjusted odds ratios (ORs) for associations between autism and retrospectively collected maternal vitamin intake before and during pregnancy. We explored interaction effects with functional genetic variants involved in one-carbon metabolism (MTHFR, COMT, MTRR, BHMT, FOLR2, CBS, and TCN2) as carried by the mother or child. Mothers of children with autism were less likely than those of typically developing children to report having taken prenatal vitamins during the three months before pregnancy or the first month of pregnancy (OR = 0.62 [95% confidence interval = 0.42–0.93]). Significant interaction effects were observed for maternal MTHFR 677 TT, CBS rs234715 GT+TT, and child COMT 472 AA genotypes, with greater risk for autism when mothers did not report taking prenatal vitamins periconceptionally (4.5 [1.4–14.6]; 2.6 [1.2–5.4]; and 7.2 [2.3–22.4], respectively). Greater risk was also observed for children whose mothers had other one-carbon metabolism pathway gene variants and reported no maternal prenatal vitamin intake. Periconceptional use of prenatal vitamins may reduce the risk of having children with autism, especially for genetically susceptible mothers and children. Replication and mechanistic investigations are warranted.