Takahashi Sakae, Cui Yu-hu, Han Yong-hua, Fagerness Jesen A, Galloway Brian, Shen Yu-cun, Kojima Takuya, Uchiyama Makoto, Faraone Stephen V, Tsuang Ming T
Division of Psychiatry, Department of Psychiatry, Nihon University, School of Medicine, Tokyo, Japan.
Schizophr Res. 2008 Sep;104(1-3):153-64. doi: 10.1016/j.schres.2008.05.028. Epub 2008 Jul 16.
Prior work found the APOL1, 2 and 4 genes, located on chromosome 22q12.3-q13.1, to be upregulated in brains of schizophrenic patients. We performed a family-based association study using 130 SNPs tagging the APOL gene family (APOL1-6). The subjects were 112 African-American (AA), 114 European-American (EA), 109 Chinese (Ch) and 42 Japanese (Jp) families with schizophrenia (377 families, 1161 genotyped members and 647 genotyped affected in total). Seven SNPs had p-values<0.05 in the APOL1, 2 and 4 regions for the AA, EA and combined (AA and EA) samples. In the AA sample, two SNPs, rs9610449 and rs6000200 showed low p-values; and a haplotype which comprised these two SNPs yielded a p-value of 0.00029 using the global test (GT) and the allele specific test (AST). The two SNPs and the haplotype were associated with risk for schizophrenia in African-Americans. In the combined (AA and EA) sample, two SNPs, rs2003813 and rs2157249 showed low p-values; and a three SNP haplotype including these two SNPs was significant using the GT (p=0.0013) and the AST (p=0.000090). The association of this haplotype with schizophrenia was significant for the entire (AA, EA, Ch and Jp) sample using the GT (p=0.00054) and the AST (p=0.00011). Although our study is not definitive, it suggests that the APOL genes should be more extensively studied in schizophrenia.
先前的研究发现，位于22号染色体q12.3 - q13.1区域的APOL1、2和4基因在精神分裂症患者的大脑中表达上调。我们进行了一项基于家系的关联研究，使用130个单核苷酸多态性（SNP）标记APOL基因家族（APOL1 - 6）。研究对象为112个患有精神分裂症的非裔美国人（AA）家庭、114个欧裔美国人（EA）家庭、109个中国人（Ch）家庭和42个日本人（Jp）家庭（共377个家庭，1161名基因分型成员，其中647名基因分型患者）。在非裔美国人、欧裔美国人以及合并样本（非裔美国人和欧裔美国人）中，APOL1、2和4区域有7个SNP的p值<0.05。在非裔美国人样本中，两个SNP，rs9610449和rs6000200显示出较低的p值；使用全局检验（GT）和等位基因特异性检验（AST），由这两个SNP组成的单倍型的p值为0.00029。这两个SNP和单倍型与非裔美国人患精神分裂症的风险相关。在合并样本（非裔美国人和欧裔美国人）中，两个SNP，rs2003813和rs2157249显示出较低的p值；使用GT（p = 0.0013）和AST（p = 0.000090），包含这两个SNP的三个SNP单倍型具有显著性。使用GT（p = 0.00054）和AST（p = 0.00011），该单倍型与精神分裂症的关联在整个样本（非裔美国人、欧裔美国人、中国人和日本人）中具有显著性。尽管我们的研究并非结论性的，但它表明APOL基因在精神分裂症方面应得到更广泛的研究。
