Proopiomelanocortin (POMC) sequencing and developmental delay: Preliminary evidence for a SNP in the 3' UTR region of the POMC gene-Possible relevance for biological risk and self-injurious behavior.
Proopiomelanocortin (POMC) sequencing and developmental delay: Preliminary evidence for a SNP in the 3' UTR region of the POMC gene-Possible relevance for biological risk and self-injurious behavior.
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阿黑皮质素原 (POMC) 测序和发育迟缓：POMC 基因 3 UTR 区域中 SNP 的初步证据 - 可能与生物风险和自残行为相关。
DOI：
10.1017/s0954579418000718
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发表时间：
2019
影响因子：
3.3
通讯作者：
Symons,FrankJ
中科院分区：
文献类型：
--
作者：
Damerow,JohnA;Tervo,RaymondC;Ehrhardt,Michael;Panoskaltsis-Mortari,Angela;Symons,FrankJ
propropiomelanocortin （POMC）分子与神经发育障碍的自伤行为（SIB）模型有关，但从未对其进行特异性测序以寻找碱基特异性多态性。本初步研究的实证重点是对11名有全面发育迟缓临床问题的儿童（平均年龄41.8个月，范围12-60个月，73%为男性）的POMC基因进行测序，其中5名有自残报告。从血样中提取基因组DNA，通过聚合酶链反应，用特异性寡核苷酸引物扩增POMC基因。扩增的基因产物由明尼苏达大学基因组中心测序，并使用Sequencher软件对结果进行分析。在两个样本（其中一个患有SIB）的3 '非翻译区（UTR）中发现了一个单核苷酸多态性（SNP） 1130 C>T。TargetScanHuman程序用于预测该突变的功能。变体c.1130预测C<T位于两个microRNAs （miRNAs； hsa-mir-3715和hsa-mir-1909）的靶位，变异等位基因T可能导致两个miRNAs的最小自由能增加。需要进一步开展更大样本的工作，以继续调查POMC作为发育迟缓/残疾儿童SIB发展的风险因素的可能功能。本研究结果表明，在3'UTR中发现的SNP可以改变mirna与POMC 3'UTR的结合，从而增加POMC的表达，并影响与自伤生物学高度相关的几种生物系统。SIB组β-内啡肽水平（M = 169.25 pg/mL）与非SIB组（M = 273.5 pg/mL, SD = 15.2）比较差异有统计学意义（p < 0.01）。干预的意义与先前观察到的SIB反应者和对阿片类拮抗剂纳曲酮治疗无反应者之间的个体差异有关。通过POMC突变状态对SIB患者进行分层可能提供一个潜在的类似定制的变量，以指导选择谁更（或更少）可能对阿片类拮抗剂治疗有反应。目前，阿片类拮抗剂治疗SIB是经验性的（试验和错误）。
The proopiomelanocortin (POMC) molecule has been implicated in models of self-injurious behavior (SIB) in neurodevelopmental disorders, but it has never been specifically sequenced in search of base specific polymorphisms. The empirical focus of this preliminary study was to sequence the POMC gene in 11 children (mean age = 41.8 months, range = 12–60 months; 73% male) with clinical concerns regarding global developmental delay, 5 with reported self-injury. Genomic DNA was extracted from blood samples, and the POMC gene was amplified by specific oligonucleotide primers via polymerase chain reaction. The amplified gene products were sequenced by the University of Minnesota Genomic Center, and the results were analyzed using Sequencher software. A single nucleotide polymorphism (SNP), 1130 C>T, was found in the 3’ untranslated region (UTR) of two samples (one of whom had SIB). The program TargetScanHuman was used to predict the function of this mutation. Variant c.1130 C<T was predicted to be located in the target site of two microRNAs (miRNAs; hsa-mir-3715 and hsa-mir-1909), and the variant allele T may result in an increased minimum free energy for the two miRNAs. Further work with much larger samples is needed to continue the investigation of POMC’s possible function as a risk factor for the development of SIB in children with developmental delay/disability. The findings presented in this study show that the SNP found in the 3’ UTR could alter the binding of miRNAs to POMC 3'UTR, thus, increasing POMC expression and affecting several biological systems with high relevance to the biology of self-injury. There was a significant difference in β-endorphin levels between SIB (M = 169.25 pg/mL) and no SIB (M = 273.5 pg/mL, SD = 15.2) cases (p < .01). Intervention implications are tied to prior observations of individual differences among SIB responders and nonresponders to treatment with the opioid antagonist naltrexone. Stratifying individuals with SIB by POMC mutation status may provide a potential tailoring-like variable to guide the selection of who is more (or less) likely to respond to opiate antagonist treatment. Currently, opioid antagonistic treatment for SIB is empiric (trial and error).