非裔美国人队列中功能性68碱基对重复序列与大麻暴露的性别特异性关联。
Gender-specific association of functional 68 bp repeats with cannabis exposure in an African American cohort.
作者信息
Yuferov Vadim, Butelman Eduardo R, Kreek Mary Jeanne
机构信息
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
出版信息
Neuropsychiatr Dis Treat. 2018 Apr 16;14:1025-1034. doi: 10.2147/NDT.S159954. eCollection 2018.
BACKGROUND
Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC), a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC.
METHODS
In this case-control study of adult African Americans (n=476; 206 females, 270 males), we examined the association of the functional prodynorphin 68 bp ( 68 bp) promoter repeats with categorical diagnoses of cannabis dependence ( criteria), as well as with a rapid dimensional measure of maximum lifetime cannabis exposure (the Kreek-McHugh-Schluger-Kellogg cannabis scale).
RESULTS
The 68 bp genotype (examined as short-short [SS], short-long [SL], or long-long [LL], based on the number of repeats) was not significantly associated with categorical cannabis-dependence diagnoses, either in males or in females. However, in males, the 68 bp SS+SL genotype was associated with both greater odds of any use of cannabis (<0.05) and earlier age of first cannabis use, compared to the LL genotype (ie, 15 versus 16.5 years of age; <0.045). Males in the SS+SL group also had greater odds of high lifetime exposure to cannabis, compared to the LL group (<0.045). Of interest, none of the aforementioned genetic associations were significant in females.
CONCLUSION
This study provides the first data on how the 68 bp genotype is associated with gender-specific patterns of exposure to cannabis. Overall, this study shows that 68 bp polymorphisms affect behaviors involved in early stages of nonmedical cannabis use and potentially lead to increasing self-exposure. These data may eventually lead to improvements in personalized medicine for the prevention and treatment of highly prevalent CUDs and neuropsychiatric comorbidities.
背景
大麻使用障碍（CUDs）会导致大量神经精神疾病及共病。有证据表明CUDs存在基于性别的差异，例如，男性患病率高于女性。大麻的主要活性成分是Δ9 - 四氢大麻酚（Δ9 - THC），它是1型大麻素受体的部分激动剂。临床前研究表明，κ阿片受体/强啡肽系统的基因或药理学操作可调节Δ9 - THC的作用。
方法
在这项针对成年非裔美国人（n = 476；206名女性，270名男性）的病例对照研究中，我们研究了功能性强啡肽原68 bp启动子重复序列与大麻依赖的分类诊断（标准）以及最大终身大麻暴露的快速量化指标（克里克 - 麦克休 - 施卢格 - 凯洛格大麻量表）之间的关联。
结果
68 bp基因型（根据重复次数分为短 - 短[SS]、短 - 长[SL]或长 - 长[LL]）与男性或女性的大麻依赖分类诊断均无显著关联。然而，在男性中，与LL基因型相比，68 bp SS + SL基因型与使用大麻的更高几率（<0.05）以及更早的首次使用大麻年龄相关（即，15岁对16.5岁；<0.045）。与LL组相比，SS + SL组的男性终身高剂量暴露于大麻的几率也更高（<0.045）。有趣的是，上述基因关联在女性中均不显著。
结论
本研究提供了关于68 bp基因型如何与特定性别的大麻暴露模式相关联的首个数据。总体而言，本研究表明68 bp多态性会影响非医疗用大麻早期阶段的行为，并可能导致自我暴露增加。这些数据最终可能会改善针对高度流行的CUDs及神经精神共病的预防和治疗的个性化医疗。
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