Association Analysis of Neuronal Nitric Oxide Synthase 1 Gene Polymorphism With Psychopathological Symptoms in Chronic Ketamine Users.

Association Analysis of Neuronal Nitric Oxide Synthase 1 Gene Polymorphism With Psychopathological Symptoms in Chronic Ketamine Users.
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DOI:
10.3389/fpsyt.2020.580771
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发表时间:
2020
影响因子:
4.7
通讯作者:
He H
He H
中科院分区:
医学3区
文献类型:
--
作者:
Chen J;Zhang M;Zhou C;Ding Y;Fan N;He H

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目的:我们以前发现,长期使用氯胺酮与各种精神病和认知症状模仿精神分裂症。NMDA受体的阻断和随后的一氧化氮合酶1(NOS 1)功能障碍被发现与精神分裂症密切相关,包括NOS 1基因多态性。我们检测了中国人群中慢性氯胺酮使用者神经元型一氧化氮合酶1(NOS 1)基因的等位基因变异,并分析了NOS 1基因多态性与慢性氯胺酮使用者精神病理症状之间的关联。NOS 1多态性与氯胺酮使用特征之间的关联也进行了研究。方法:197名男性氯胺酮慢性使用者和82名对照者。使用TaqMan®检测系统,通过实时PCR检测NOS 1基因的4种常见SNP:rs6490121、rs 41279104、rs3782206和rs3782219。采用阳性和阴性症状量表(PANSS)、贝克抑郁量表(BDI)和贝克焦虑量表(BAI)评估精神病理症状。结果如下:慢性氯胺酮使用者中rs6490121和rs 41279104的基因型分布与对照组有显著差异(p = 0.0001和p = 0.002)。氯胺酮使用者rs6490121的G等位基因频率高于对照组(p = 2.23 * 10−6,OR = 3.07,95%CI = 1.93-4.90)。rs 41279104位点T等位基因频率在氯胺酮慢性使用者中高于对照组(P = 0.01,OR = 1.76,95%CI = 1.14-2.72)。氯胺酮使用者中rs6490121的三个基因型组之间的BAI评分存在显著差异(F = 6.21,p = 0.002);基因型AG和GG的受试者的评分低于基因型AA的受试者。PANSS阴性症状子量表评分在rs 41279104的三个基因型组之间存在显著差异(F = 5.39,p = 0.005);在氯胺酮使用者中,CT和TT基因型受试者的评分高于CC基因型受试者。氯胺酮使用者NOS 1基因4个多态性位点的不同基因型的用药特征无差异(p > 0.05)。
Objective: We previously found that chronic ketamine usages were associated with various psychotic and cognitive symptoms mimicking schizophrenia. The blockade of the NMDA receptor and subsequent nitric oxide synthase 1 (NOS1) dysfunction were found to be closely correlated with schizophrenia including NOS1 gene polymorphisms. We examined the allelic variants of the gene coding neuronal nitric oxide synthase 1 (NOS1) in chronic ketamine users in the Chinese population and analyzed the association between NOS1 gene polymorphism and psychopathological symptoms in chronic ketamine users. The association between the NOS1 polymorphism and ketamine use characteristics was also examined. Methods: One hundred ninety seven male chronic ketamine users and 82 controls were recruited. Four common SNPs of the NOS1 gene, rs6490121, rs41279104, rs3782206, and rs3782219, were examined by real-time PCR with the TaqMan® assay system. Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI). Results: The genotype distribution of rs6490121 and rs41279104 in chronic ketamine users was significantly different from that in the control (p = 0.0001 and p = 0.002). The G allele frequency of rs6490121 in ketamine users was higher than that in the control (p = 2.23 * 10−6, OR = 3.07, 95% CI = 1.93–4.90). The T allele frequency of rs41279104 in chronic ketamine users was higher than that in the control (p = 0.01, OR = 1.76, 95% CI = 1.14–2.72). The BAI score was significantly different among the three genotypic groups of rs6490121 (F = 6.21, p = 0.002) in ketamine users; subjects of genotype AG and GG had a lower score than subjects of genotype AA. The score of the negative symptom subscale of PANSS was significantly different among the three genotypic groups of rs41279104 (F = 5.39, p = 0.005); in ketamine users, subjects of genotype CT and TT had a higher score than subjects of genotype CC. There was no difference in drug use characteristics in different genotypes of the four NOS1 gene polymorphisms tested in ketamine users (p > 0.05).
DOI: 10.1016/s0893-133x(01)00243-3
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