VNTR polymorphism in the monoamine oxidase A promoter region and cerebrospinal fluid catecholamine concentrations in forensic autopsy cases
VNTR polymorphism in the monoamine oxidase A promoter region and cerebrospinal fluid catecholamine concentrations in forensic autopsy cases
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DOI：
10.1016/j.neulet.2019.02.029
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发表时间：
2019-05-14
影响因子：
2.5
通讯作者：
Ishikawa, Takaki
中科院分区：
文献类型：
--
作者：
Matsusue, Aya;Kubo, Shin-ichi;Ishikawa, Takaki
单胺氧化酶A(MAOA)在儿茶酚胺代谢中起重要作用，调节肾上腺素能、去甲肾上腺素能和多巴胺能信号。MAOA外显子1上游约1.2kb处有一个多态启动子可变数目串联重复序列(VNTR)基因座(MAOA-uVNTR)。功能研究表明，MAOA-uVNTR影响基因表达。在本研究中，我们检测了未检测到安非他明或精神药物的日本尸检病例中MAOA-uVNTR等位基因的频率。总共对87名男性和35名女性进行了评估和调查，以了解MAOA-uVNTR基因多态对脑脊液(CSF)儿茶酚胺浓度的可能影响。在男性中，MAOA-uVNTR多态与脑脊液肾上腺素(ADR)、去甲肾上腺素(Nad)或多巴胺(DA)水平无显著关联。相反，3重复等位基因纯合子(即3/3携带者)的脑脊液中ADR(p=0.024)和DA(p=0.035)水平高于4重复等位基因杂合子和纯合子个体(分别为3/4和4/4)。我们未发现女性MAOA-uVNTR基因多态与脑脊液Nad水平显著相关。因此，本研究结果表明，MAOA-uVNTR基因多态性影响女性脑脊液ADR和DA水平。
Monoamine oxidase A (MAOA) plays important roles in the metabolism of catecholamines and modulates adrenergic, noradrenergic, and dopaminergic signaling. A polymorphic promoter variable number tandem repeat (VNTR) locus (MAOA-uVNTR) is located approximately 1.2 kb upstream from MAOA exon 1. Functional studies revealed that MAOA-uVNTR affects gene expression. In the present study, we examined the frequencies of MAOA-uVNTR alleles in Japanese autopsy cases, in which amphetamines or psychotropic drugs were not detected. In total, 87 males and 35 females were evaluated and investigated for the possible effect of MAOA-uVNTR polymorphisms on cerebrospinal fluid (CSF) catecholamine concentrations. In males, there was no significant association between MAOA-uVNTR polymorphisms and CSF adrenaline (Adr), noradrenaline (Nad), or dopamine (DA) levels. In contrast, females who were homozygous for the 3-repeat allele (i.e., 3/3 genotype carriers) had higher CSF levels of Adr (p = 0.024) and DA (p = 0.035) than individuals who were heterozygous or homozygous for the 4-repeat allele (3/4 and 4/4, respectively). We found no significant association between MAOA-uVNTR polymorphisms and CSF Nad levels in females. Thus, the results of the present study indicated that MAOA-uVNTR polymorphism influences CSF Adr and DA levels in females.