Küçükali Cem Ismail, Ulusoy Canan, Özkan Özden, Orhan Nurcan, Güleç Hüseyin, Erdağ Ece, Buker Seda, Tüzün Erdem
Department of Neuroscience, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey
Department of Neuroscience, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
In Vivo. 2015 Jan-Feb;29(1):103-8.
Bipolar disorder (BD) has a complex genetic etiology, with multiple unidentified genes and environmental factors playing important roles in its pathogenesis. A growing body of evidence suggests that reactive oxygen species (ROS) may be crucially involved in the pathogenesis of psychiatric diseases, including BD. The association between paraoxonase 1 (PON1), an important antioxidant enzyme, and development of BD has been scarcely investigated. We thus attempted to examine genetic variants in the PON1 gene, a putative BD susceptibility gene, in patients with bipolar disease and their first-degree relatives.
The study population consisted of 292 healthy individuals, 199 patients with BD, and 280 unaffected first-degree relatives of the patients. Genotyping of PON1 L55M and Q192R polymorphisms was performed by polymerase chain reaction and restriction enzyme digestion.
Patients mostly shared the same PON1 genotypes with their first-degree relatives. The frequency of MM genotype of PON1 L55M polymorphism was lower and that of LM genotype was higher in patients and relatives than healthy controls. PON1 enzyme activities did not differ between patient, relative and healthy control groups but were influenced by PON1 genotype.
Our findings indicate an association between the genetic variants of PON1 and BD. The PON1 L55M MM genotype seems to be protective against the development of BD.
双相情感障碍(BD)具有复杂的遗传病因,多种未确定的基因和环境因素在其发病机制中起重要作用。越来越多的证据表明,活性氧(ROS)可能在包括BD在内的精神疾病发病机制中起关键作用。对重要抗氧化酶对氧磷酶1(PON1)与BD发病之间的关联研究甚少。因此,我们试图检测双相情感障碍患者及其一级亲属中PON1基因(一种假定的BD易感基因)的遗传变异。
研究人群包括292名健康个体、199名BD患者以及280名患者的未患病一级亲属。通过聚合酶链反应和限制性酶切对PON1 L55M和Q192R多态性进行基因分型。
患者与其一级亲属大多共享相同的PON1基因型。与健康对照相比,患者及其亲属中PON1 L55M多态性的MM基因型频率较低,而LM基因型频率较高。患者组、亲属组和健康对照组之间的PON1酶活性无差异,但受PON1基因型影响。
我们的研究结果表明PON1基因变异与BD之间存在关联。PON1 L55M的MM基因型似乎对BD的发生具有保护作用。