A resistance gene in disguise for schizophrenia?
A resistance gene in disguise for schizophrenia?
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DOI：
10.1002/ajmg.b.30365
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发表时间：
2007-03-05
影响因子：
2.8
通讯作者：
Yoshikawa, Takeo
中科院分区：
文献类型：
--
作者：
Doi, Nagafumi;Itokawa, Masanari;Yoshikawa, Takeo
我们研究了一个假设，即-485 T，一个新的多态性的神经肽Y基因的启动子区，这是与精神分裂症在我们以前的文件，赋予疾病的易感性。在一项病例对照关联研究中，招募了331名无关的日本精神分裂症患者（S-1：先前研究中较轻的病例，n = 212; S-2：其他较重的病例，n = 119）和199名无关的正常对照。通过（1）比较一般人群中每种基因型的风险，（2）检测-485 T的基因剂量与用阳性和阴性症状量表评估的S2慢性结局严重程度之间的相关性，（3）比较三种基因型在S-1 + S-2期发病年龄的分布。-485 T与S-1 + S-2中的精神分裂症显著相关。基因剂量与症状评分呈显著负相关。晚发型组中-485T纯合子出现第二个高峰频率，早发组中交替等位基因纯合子出现单峰频率。在一般人群中，-485 T杂合子比纯合子患精神分裂症的风险更高，这不支持与易感基因连锁不平衡的可能性。-485 T最可能赋予精神分裂症抗性，但不赋予精神分裂症易感性。核抗性基因和线粒体DNA中假定的致病基因之间的相互作用被提出。(c)2006 Wiley-Liss，Inc.
We examined the hypothesis that -485 T, a novel polymorphism in the promoter region of the neuropeptide Y gene which was shown to be associated with schizophrenia in our previous paper, confers susceptibility to the disease. For a case-control association study, 331 unrelated Japanese schizophrenics (S-1: milder cases in the previous study, n = 212; and S-2: additional severer cases, n = 119) and 199 unrelated normal controls were recruited. Contribution of -485 T to the risk and the severity of the illness was examined by (1) comparing the risk in each genotype in the general population, (2) testing correlations between the gene-dose of -485 T, and the severity of chronic outcome in S2 assessed with the Positive and Negative Symptom Scale, and (3) comparing the distribution of age at onset in S-1 + S-2 among the three genotypes. -485 T was significantly associated with schizophrenia in S-1 + S-2. Significant negative correlations were observed between the gene-dose and the symptom assessment scores in all items. The homozygote of -485 T showed a second peak frequency in the late-onset group both in males and females, while the homozygote of the alternative allele showed a single peak in the early-onset group. The higher risk of schizophrenia in the heterozygote than in the homozygote of -485 T in the general population did not support the possibility of linkage disequilibrium with a susceptibility gene. -485 T most likely confers resistance but not susceptibility to schizophrenia. An interaction between a nuclear resistance gene and a presumptive pathogenic gene in the mitochondrial DNA was suggested. (c) 2006 Wiley-Liss, Inc.