β2-adrenergic receptor activation and genetic polymorphisms in autism:: Data from dizygotic twins
β2-adrenergic receptor activation and genetic polymorphisms in autism:: Data from dizygotic twins
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DOI：
10.1177/08830738050200110401
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发表时间：
2005-11-01
影响因子：
1.9
通讯作者：
Zimmerman, AW
中科院分区：
文献类型：
--
作者：
Connors, SL;Crowell, DE;Zimmerman, AW
妊娠期和遗传因素可以通过对胎儿大脑发育的影响而导致婴儿期和幼儿期的自闭症。先前的双胞胎研究表明，自闭症的发展有很强的遗传因素，这种疾病可能有多种原因。我们研究了暴露于特布他林的异卵双胞胎产前过度刺激β(2)-肾上腺素能受体的影响，特布他林是一种选择性β(2)-肾上腺素能受体激动剂，用于治疗早产，作为妊娠因素。作为可能的遗传机制，我们研究了DNA可获得的双胞胎β(2)-肾上腺素能受体的两种多态性：密码子16 （16G）的甘氨酸替代和密码子27 （27E）的谷氨酸替代，与野生型受体相比，它们在体内的脱敏性降低。连续使用特布他林2周或更长时间与异卵双胞胎自闭症谱系障碍的一致性增加相关（相对风险= 2.0），对于没有其他兄弟姐妹受影响的男性双胞胎，风险进一步增加（相对风险= 4.4）。与人群对照相比，自闭症患者中16G和27E多态性存在显著相关性（P = 0.006）。产前使用特布他林过度刺激β(2)-肾上腺素能受体，或增加β(2)-肾上腺素能受体脱敏性降低的遗传多态性信号，可影响胎儿大脑的细胞反应和发育程序，导致自闭症。
Gestational and genetic factors can contribute to autism during infancy and early childhood through their effects on fetal brain development. Previous twin studies have shown strong genetic components for the development of autism, a disorder that can have multiple causes. We investigated the effects of prenatal overstimulation of the beta(2)-adrenergic receptor in dizygotic twins who were exposed to terbutaline, a selective beta(2)-adrenergic receptor agonist used to treat premature labor, as a gestational factor. As a possible genetic mechanism, we studied two beta(2)-adrenergic receptor polymorphisms in twins from whom DNA was available: glycine substitution at codon 16 (16G) and glutamic acid substitution at codon 27 (27E), which show diminished desensitization in vivo compared with the wild-type receptor. Continuous terbutaline exposure for 2 weeks or longer was associated with increased concordance for autism spectrum disorders in dizygotic twins (relative risk = 2.0), with a further increase in the risk for male twins with no other affected siblings (relative risk = 4.4). A significant association was found between the presence of 16G and 27E polymorphisms in autistic patients compared with population controls (P = .006). Prenatal overstimulation of the beta(2)-adrenergic receptor by terbutaline or by increased signaling of genetic polymorphisms of the beta(2)-adrenergic receptor that have diminished desensitization can affect cellular responses and developmental programs in the fetal brain, leading to autism.