Department of Pediatrics, University of Texas Medical School at Houston, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
PLoS One. 2012;7(12):e51330. doi: 10.1371/journal.pone.0051330. Epub 2012 Dec 5.
The objective of this study was to examine the relation between the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and behaviors related to attention- deficit/hyperactivity disorder (ADHD) in individuals with myelomeningocele. The rationale for the study was twofold: folate metabolizing genes, (e.g. MTHFR), are important not only in the etiology of neural tube defects but are also critical to cognitive function; and individuals with myelomeningocele have an elevated incidence of ADHD. Here, we tested 478 individuals with myelomeningocele for attention-deficit hyperactivity disorder behavior using the Swanson Nolan Achenbach Pelham-IV ADHD rating scale. Myelomeningocele participants in this group for whom DNAs were available were genotyped for seven single nucleotide polymorphisms (SNPs) in the MTHFR gene. The SNPs were evaluated for an association with manifestation of the ADHD phenotype in children with myelomeningocele. The data show that 28.7% of myelomeningocele participants exhibit rating scale elevations consistent with ADHD; of these 70.1% had scores consistent with the predominantly inattentive subtype. In addition, we also show a positive association between the SNP rs4846049 in the 3'-untranslated region of the MTHFR gene and the attention-deficit hyperactivity disorder phenotype in myelomeningocele participants. These results lend further support to the finding that behavior related to ADHD is more prevalent in patients with myelomeningocele than in the general population. These data also indicate the potential importance of the MTHFR gene in the etiology of the ADHD phenotype.
本研究旨在探讨 5,10-亚甲基四氢叶酸还原酶（MTHFR）基因与脑脊膜膨出患者注意力缺陷多动障碍（ADHD）相关行为之间的关系。本研究的理论基础有二：一方面，叶酸代谢基因（如 MTHFR）不仅在神经管缺陷的发病机制中非常重要，而且对认知功能也至关重要；另一方面，脑脊膜膨出患者的 ADHD 发病率较高。在此，我们使用 Swanson Nolan Achenbach Pelham-IV ADHD 评定量表对 478 名脑脊膜膨出患者进行了 ADHD 行为测试。在该组中，我们对有可用 DNA 的脑脊膜膨出患者进行了 MTHFR 基因中七个单核苷酸多态性（SNP）的基因分型。评估了这些 SNP 与脑脊膜膨出患儿 ADHD 表型表现的相关性。数据显示，28.7%的脑脊膜膨出患者表现出与 ADHD 一致的量表升高；其中 70.1%的患者表现出主要注意力不集中的亚型。此外，我们还发现 MTHFR 基因 3'-非翻译区中的 SNP rs4846049 与脑脊膜膨出患者的注意力缺陷多动障碍表型之间存在正相关。这些结果进一步支持了以下发现，即与 ADHD 相关的行为在脑脊膜膨出患者中比在普通人群中更为普遍。这些数据还表明 MTHFR 基因在 ADHD 表型的发病机制中具有潜在的重要性。
