The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning.
The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning.
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DOI：
10.1007/s13365-014-0241-y
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发表时间：
2014-06
影响因子：
3.2
通讯作者：
Sacktor, Ned
中科院分区：
文献类型：
--
作者：
Levine, Andrew J.;Reynolds, Sandra;Cox, Christopher;Miller, Eric N.;Sinsheimer, Janet S.;Becker, James T.;Martin, Eileen;Sacktor, Ned
HIV-1感染和非法使用兴奋剂都会对神经认知功能产生不利影响，这些影响可能是叠加的。然而，存在显著的可变性，例如尚未确定的外源性和内源性因素会影响神经认知障碍的风险。HIV和兴奋剂的文献都表明，宿主免疫和多巴胺相关基因的遗传变异是一个这样的因素。在这项研究中，HIV状态、兴奋剂使用和基因型对神经认知功能的个体和相互作用进行了长达10年的纵向研究。来自多中心艾滋病队列研究的952例高加索HIV+和HIV -病例被纳入研究。所有病例在1985年至1995年间至少进行了两次全面的神经认知评估。为了避免不同药物方案的混淆效应，对haart前的数据进行了检查。采用线性混合模型，以神经认知领域评分作为结果变量。没有发现4向相互作用，表明HIV和兴奋剂的使用不会随着时间的推移相互作用，影响神经认知功能作为基因型的功能。发现基因型和HIV状态之间存在多种3向相互作用。所有发现与HIV状态相互作用的免疫相关基因都在预期的方向上影响神经认知功能；然而，只有CCL2和CCL3特异性地影响HIV+个体。多巴胺相关的基因变异通常只影响hiv阴性个体。同时使用兴奋剂的HIV阳性个体的神经认知功能与不使用兴奋剂的人没有显著差异。这些发现支持了CCL2和CCL3的免疫相关遗传差异在HIV+个体神经认知功能中的作用；然而，它们的影响很小。与另一个队列的发现一致，da相关的遗传差异似乎不会影响HIV+个体的纵向神经认知功能。
Both HIV-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect ones risk for neurocognitive impairment. Both HIV and stimulant literature indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning was examined longitudinally over a 10 year period. 952 Caucasian HIV+ and HIV− cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-HAART data was examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. No 4-way interactions were found, indicating that HIV and stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple 3-way interactions were found that involved genotype and HIV status. All immunologic-related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only CCL2 and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. The findings support the role of immunologic-related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however their impact is minor. Consistent with findings from another cohort, DA-related genetic differences do not appear to impact the longitudinal neurocognitive functioning of HIV+ individuals.
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DOI：
10.1073/pnas.111134598
发表时间：
2001-06-05
影响因子：
11.1
作者：
Egan, MF;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR
DOI：
10.1076/jcen.25.7.893.16489
发表时间：
2003-10-01
影响因子：
2.2
作者：
Basso, MR;Bornstein, RA
通讯作者：
Bornstein, RA
影响因子：
11
作者：
Daly, G;Hawi, Z;Gill, M
通讯作者：
Gill, M
DOI：
10.1073/pnas.0803526105
发表时间：
2008-06-24
影响因子：
11.1
作者：
Burt, Trevor D.;Agan, Brian K.;Ahuja, Sunil K.
通讯作者：
Ahuja, Sunil K.
影响因子：
4.4
作者：
Carey, CL;Woods, SP;Grant, I
通讯作者：
Grant, I