Kishi Taro, Ikeda Masashi, Kitajima Tsuyoshi, Yamanouchi Yoshio, Kinoshita Yoko, Kawashima Kunihiro, Okochi Tomo, Inada Toshiya, Ozaki Norio, Iwata Nakao
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.
J Neural Transm (Vienna). 2008 Oct;115(10):1457-61. doi: 10.1007/s00702-008-0114-8. Epub 2008 Sep 2.
Several lines of evidence suggest that nicotinic cholinergic dysfunction may contribute to the cognitive impairments in schizophrenia. The majority of high affinity nicotine binding sites in the human brain have been implicated in heteropentameric alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptors; therefore, these two neuronal nicotinic acetylcholine receptors genes (CHRNA4 and CHRNB2) are considered to be attractive candidate genes for the pathophysiology of schizophrenia. To represent these two genes in a gene-wide manner, we first evaluated the linkage disequilibrium structure using our own control samples. Thirteen SNPs (7 SNPs for CHRNA4 and 5 SNPs for CHRNB2) were selected as tagging SNPs. Using these tagging SNPs, we then conducted genetic association analysis of case-control samples (738 schizophrenia and 753 controls) in the Japanese population. No significant association was detected in the allele/genotype-wise or haplotype-wise analysis. Our results suggest that CHRNA4 and CHRNB2 do not play a major role in Japanese schizophrenia.
多条证据表明，烟碱型胆碱能功能障碍可能导致精神分裂症的认知障碍。人类大脑中大多数高亲和力尼古丁结合位点与神经元烟碱型乙酰胆碱受体的异源五聚体α4和β2亚基有关；因此，这两个神经元烟碱型乙酰胆碱受体基因（CHRNA4和CHRNB2）被认为是精神分裂症病理生理学的有吸引力的候选基因。为了在全基因范围内研究这两个基因，我们首先使用我们自己的对照样本评估连锁不平衡结构。选择了13个单核苷酸多态性（CHRNA4的7个单核苷酸多态性和CHRNB2的5个单核苷酸多态性）作为标签单核苷酸多态性。然后，使用这些标签单核苷酸多态性，我们对日本人群中的病例对照样本（738例精神分裂症患者和753例对照）进行了基因关联分析。在等位基因/基因型分析或单倍型分析中均未检测到显著关联。我们的结果表明，CHRNA4和CHRNB2在日本精神分裂症中不发挥主要作用。
