Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
Compr Psychiatry. 2016 Oct;70:118-24. doi: 10.1016/j.comppsych.2016.07.004. Epub 2016 Jul 9.
Patients with schizophrenia are more likely to be smokers than the general population, which makes them an interesting group with which to study the etiology of nicotine dependency. We studied the prevalence of a gene variant of peroxisome proliferator-activated receptor alpha (PPARα) in schizophrenia, together with nicotine dependency, to investigate whether the PPARα-L162V polymorphism (rs1800206) influences nicotine dependency in schizophrenia. Given evidence suggesting that smoking influences the severity of schizophrenia, together with our recent data linking the PPARα-L162V polymorphism to clinical manifestations of schizophrenia (in the Croatian population), we hypothesized that interactions between the two (smoking and the PPARα-L162V polymorphism) might contribute to disease onset and scores for the Positive and Negative Syndrome Scale. To the best of our knowledge, this is the first study to investigate the possible associations between the PPARα gene and nicotine dependency.
Genotyping was performed for 267 chronically ill schizophrenia patients (males/females: 140/127) by polymerase chain reaction.
A significant excess of PPARα-L162V genotypes and PPARα-162V alleles were detected among female smokers in comparison to female nonsmokers (18.2% vs. 2.0%, and 9.1% vs. 1.0%, p<0.01, respectively). We also revealed a significant PPARα genotype-smoking interaction that predicted positive symptom severity among male patients (F=4.43, p<0.05). These data indicated that the PPARα-L162V heterozygous genotype, depending on smoking status, might be of relevance as either protective, or a risk factor, for the severity of positive symptoms. No interaction between the PPARα-L162V polymorphism and smoking for the time of onset of schizophrenia was detected (p>0.05, respectively).
We demonstrated two significant yet weak effects. The first showed an effect of the PPARα-L162V polymorphism on the risk of nicotine dependency. The second linked the PPARα genotype-smoking interaction to positive symptoms severity among schizophrenia patients; both effects manifested in a gender-specific fashion.
精神分裂症患者的吸烟率高于普通人群，这使得他们成为研究尼古丁依赖病因的一个有趣群体。我们研究了过氧化物酶体增殖物激活受体α（PPARα）基因变异与精神分裂症和尼古丁依赖的相关性，以探讨 PPARα-L162V 多态性（rs1800206）是否影响精神分裂症患者的尼古丁依赖。鉴于吸烟会影响精神分裂症的严重程度，并且我们最近的数据表明 PPARα-L162V 多态性与精神分裂症的临床表现有关（在克罗地亚人群中），我们假设两者之间的相互作用（吸烟和 PPARα-L162V 多态性）可能会导致疾病的发生和阳性与阴性症状量表的评分。据我们所知，这是第一项研究 PPARα 基因与尼古丁依赖之间可能存在的关联。
通过聚合酶链反应对 267 名慢性精神分裂症患者（男性/女性：140/127）进行基因分型。
与女性非吸烟者相比，女性吸烟者中 PPARα-L162V 基因型和 PPARα-162V 等位基因明显过多（18.2%比 2.0%，9.1%比 1.0%，p<0.01）。我们还发现了一个显著的 PPARα 基因型-吸烟相互作用，它可以预测男性患者的阳性症状严重程度（F=4.43，p<0.05）。这些数据表明，PPARα-L162V 杂合基因型，取决于吸烟状态，可能是阳性症状严重程度的保护因素或危险因素。未发现 PPARα-L162V 多态性与吸烟对精神分裂症发病时间的相互作用（p>0.05，分别）。
我们证明了两个显著但较弱的效应。第一个显示了 PPARα-L162V 多态性对尼古丁依赖风险的影响。第二个将 PPARα 基因型-吸烟相互作用与精神分裂症患者的阳性症状严重程度联系起来；这两种效应都表现出性别特异性。
