Zerdazi El-Hadi, Oliveira José, Vorspan Florence, Bennabi Meriem, Jamain Stéphane, Etain Bruno, Leboyer Marion, Tamouza Ryad, Bellivier Frank
INSERM UMR-S1144 - VariaPsy, Hôpital Fernand Widal, Paris 75010, France; AP-HP, DHU Pe-PSY, Pôle de Psychiatrie et d'Addictologie des Hôpitaux Universitaires, Henri Mondor, Créteil F94000, France.
INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France.
J Neuroimmunol. 2017 Apr 15;305:96-101. doi: 10.1016/j.jneuroim.2017.01.021. Epub 2017 Feb 1.
Bipolar disorder (BD) is associated with an increased risk of tobacco dependence, the leading addictive substance worldwide. Toll-like receptor 4, a sensor of pathogens and of products of cellular stress and damage, is a major innate immune molecule and logical candidate gene for tobacco dependence in BD because (i) the involvement of TLR4 molecules in several substance use disorders has been suggested, (ii) and the association between the TLR4 gene and BD. We analysed herein the potential association between six TLR4 polymorphisms and lifetime tobacco smoking in 514 BD patients. Significant association between tobacco smoking and rs10759932 was found (genotype, Cochrane Armitage trend test, p=0.008, p=0.040 and alleles, p=0.008; p=0.040), where the C minor allele is associated with a protective effect, even after adjusting for confounding factors (OR=1.54 [1.04-2.30], p=0.03). Our results suggest that TLR4 gene polymorphism may act as an intermediate factor for the association between tobacco smoking addiction and BD.
双相情感障碍（BD）与烟草依赖风险增加有关，烟草是全球主要的成瘾物质。Toll样受体4是病原体以及细胞应激和损伤产物的传感器，是一种主要的先天免疫分子，也是BD中烟草依赖的合理候选基因，原因如下：（i）已有研究表明TLR4分子参与多种物质使用障碍；（ii）TLR4基因与BD之间存在关联。我们在此分析了514例BD患者中6种TLR4基因多态性与终生吸烟之间的潜在关联。发现吸烟与rs10759932之间存在显著关联（基因型， Cochr ane-Armitage趋势检验，p = 0.008，p = 0.040；等位基因，p = 0.008；p = 0.040），其中C等位基因具有保护作用，即使在调整混杂因素后也是如此（OR = 1.54 [1.04 - 2.30]，p = 0.03）。我们的结果表明，TLR4基因多态性可能是吸烟成瘾与BD之间关联的一个中间因素。
