An association study of the Hermansky-Pudlak syndrome type 4 gene in schizophrenic patients
An association study of the Hermansky-Pudlak syndrome type 4 gene in schizophrenic patients
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精神分裂症患者赫曼斯基-普德拉克综合征4型基因的关联研究
DOI：
10.1097/ypg.0b013e32836130a9
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Akiyama K.
中科院分区：
文献类型：
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作者：
Saito A;Kuratomi G;Ito C;Matsuoka H;Suzuki T;Ozeki Y;Watanabe T;Fujii K;Shimoda K;Fukushima Y;Inukai T;Ohmori K;Akiyama K.
目的我们遇到了两个日本兄弟姐妹，他们患有Hermansky-Pudlak综合征(HPS)和严重的精神障碍(精神分裂症和严重抑郁症)。众所周知，HPS是由人类基因HPS1到HPS8和PLDN(HPS9)中的一个局部突变引起的，HPS9编码参与内体转运途径的亚单位蛋白，在这里，我们报道了导致兄弟姐妹疾病的突变，并利用突变分析中要筛选的基因的多态性进行了精神分裂症的病例对照关联研究。方法我们分析了三个导致HPS的基因HPS1、HPS4和HPS7，以确定与兄弟姐妹有关的基因突变。对精神分裂症患者(n=422)和对照组(n=578)进行了HPS4基因全基因9个标记单核苷酸多态的病例-对照关联研究。结果两例HPS患者HPS4基因c.541C>；T(Rs119471022)无意义突变(T/T)纯合，定位于人类染色体22q12。1.在他们的母亲和另外两个兄弟姐妹中，同样的无义突变存在于杂合状态(C/T)中。Rs9608491(C/T)基因内含子4的分布有与精神分裂症相关的趋势，多项检测的校正P值为0.053。单倍型分析表明，两个座位中的两个单倍型，以及所有三个座位、四个座位和五个座位的单倍型，由于它们共享rs9608491，产生了与精神分裂症相关的显著证据，如下综合P值所示。当给rs4822724、rs61276843、rs9608491、rs713998和rs2014410这5个单倍型标记单核苷酸多态赋予序号(1、2、3、4和5)时，得到的单倍型的综合P值分别为2-3的P=0.0039、3-4的P=0.0142、1-2-3的P=0.0083、2-3-4的P=0.0187、3-4-5的P=0.0191、1-2-4-5的P=0.0270、2-3-4-5的P=0.02461-2-3-4-5为0.0261。
ObjectiveWe encountered two Japanese siblings who had Hermansky–Pudlak syndrome (HPS) and major mental disorders (schizophrenia and major depression) as well. As it is known that HPS is caused by a local mutation in one of the human genes, named HPS1 to HPS8 and PLDN (HPS9), encoding subunit proteins involved in endosomal trafficking pathways, here, we report the mutation causing the siblings disease and a case–control association study of schizophrenia using polymorphisms of a gene to be screened in the mutation analysis.MethodsWe analyzed three HPS-causing genes, HPS1, HPS4, and HPS7, to identify a genetic mutation involved in the siblings. A case–control association study of nine tagging single-nucleotide polymorphisms of the entire genetic region of the HPS4 gene resulting from the screening in the siblings was carried out for schizophrenic patients (n= 422) and controls (n= 578).ResultsThe two patients with HPS were homozygous for nonsense mutation (T/T) for the c. 541C> T (rs119471022) in the HPS4 gene, which is mapped to human chromosome 22q12. 1. The same nonsense mutation existed in the heterozygous state (C/T) in their mother and in two other siblings. The genotypic distribution of rs9608491 (C/T) in intron 4 showed a trend toward an association with schizophrenia as indicated by a corrected P-value of 0.053 controlling for multiple testing. Haplotype analyses showed that two of two-locus haplotypes, and all of three-locus, four-locus, and five-locus haplotypes, as they share rs9608491, yielded significant evidence for association with schizophrenia as shown by the following omnibus P-values. When rs4822724, rs61276843, rs9608491, rs713998, and rs2014410, five haplotype tagging single-nucleotide polymorphisms, are assigned serial numerals (1, 2, 3, 4, and 5), the omnibus P-values for the resulting haplotypes were P= 0.0039 for 2-3, P= 0.0142 for 3-4, P= 0.0083 for 1-2-3, P= 0.0187 for 2-3-4, P= 0.0191 for 3-4-5, P= 0.0270 for 1-2-3-4, P= 0.0246 for 2-3-4-5, and 0.0261 for 1-2-3-4-5.Conclusion