pcr样ER激酶(PERK)单倍型与HIV感染者的抑郁症状相关

Journal of neurology and psychology Pub Date : 2023-01-01 Epub Date: 2023-03-09 DOI:10.13188/2332-3469.1000049
S Haddadi, K L Jordan-Sciutto, C Akay-Espinoza, D Grelotti, S L Letendre, B Tang, R J Ellis
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引用次数: 0

摘要

背景:尽管抗逆转录病毒治疗(ART)能抑制病毒,但在HIV感染者(PWH)中,抑郁症是一种使人衰弱且难以治疗的疾病。抑郁症与pkr样ER激酶(PERK)途径的激活有关,该途径调节代谢应激下的蛋白质合成。我们评估了在PWH中影响PERK表达与抑郁情绪关系的常见PERK单倍型。方法:选取6个研究中心的PWH进行研究。采用TaqMan靶向测序进行基因分型。确定了PERK的主要单倍型A、B和D。采用贝克抑郁量表- ii (BDI-II)评估抑郁症状严重程度。协变量包括遗传定义的祖先、人口统计学、艾滋病毒疾病/治疗参数和抗抑郁治疗进行了评估。数据分析采用多变量回归模型。结果:共纳入287例PWH患者,平均(SD)年龄为57.1±7.8岁。虽然最大的种族群体是非西班牙裔白人(n=129, 45.3%),但非裔美国人(n=124, 43.5%)和西班牙裔(n=30, 10.5%)占了一半以上的样本。女性占20.3%,病毒抑制率为96.5%。BDI-II平均值为9.6±9.5,28.9%高于轻度抑郁的临界值(BDI-II>13)。PERK单倍型频率分别为AA57.8%、AB25.8%、AD 10.1%和BB4.88%。PERK单倍型根据遗传祖先存在差异(p=6.84e-6)。AB单倍型受试者的BDI-II得分显著高于AB单倍型(F=4.45, p=0.0007)。考虑到潜在的混淆,这一发现是强有力的。结论:PERK单倍型与PWH患者抑郁情绪相关。因此,药物靶向perk相关通路可能会改善PWH患者的抑郁。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV.

PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV.

PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV.

Background: Depression is a debilitating and difficult-to-treat condition in people with HIV (PWH) despite viral suppression on antiretroviral therapy (ART). Depression is associated with activation of the PKR-like ER kinase (PERK) pathway, which regulates protein synthesis in response to metabolic stress. We evaluated common PERK haplotypes that influence PERK expression in relation to depressed mood in PWH.

Methods: PWH from 6 research centers were enrolled in the study. Genotyping was conducted using targeted sequencing with TaqMan. The major PERK haplotypes A, B, and D were identified. Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II). Covariates including genetically-defined ancestry, demographics, HIV disease/treatment parameters and antidepressant treatments were assessed. Data were analyzed using multivariable regression models.

Results: A total of 287 PWH with a mean (SD) age of 57.1±7.8 years were enrolled. Although the largest ethnic group was non-Hispanic white (n=129, 45.3%), African-American (n=124, 43.5%) and Hispanic (n=30, 10.5%) made up over half the sample. 20.3% were female and 96.5% were virally suppressed. Mean BDI-II was 9.6±9.5, and 28.9% scored above the cutoff for mild depression (BDI-II>13). PERK haplotype frequencies were AA57.8%, AB25.8%, AD 10.1%, and BB4.88%. PERK haplotypes were differentially represented according to genetic ancestry (p=6.84e-6). BDI-II scores were significantly higher in participants with the AB haplotype (F=4.45, p=0.0007).This finding was robust to consideration of potential confounds.

Conclusion: PERK haplotypes were associated with depressed mood in PWH.Consequently, pharmacological targeting of PERK-related pathways might amelioratedepression in PWH.

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