Chavarría-Siles I, Walss-Bass C, Quezada P, Dassori A, Contreras S, Medina R, Ramírez M, Armas R, Salazar R, Leach R J, Raventos H, Escamilla M A
Psychiatric Genetics Research Center, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Mol Psychiatry. 2007 Nov;12(11):1033-41. doi: 10.1038/sj.mp.4001997. Epub 2007 Apr 17.
Schizophrenia (SC) and bipolar disorder (BP) share many clinical features, among them psychosis. We previously identified a putative gene locus for psychosis on chromosome 18p in a sample from the Central Valley of Costa Rica (CVCR) population. The present study replicated the association to a specific allele of microsatellite marker D18S63 on 18p11.3, using a newly collected sample from the CVCR. A combined analysis of both samples, plus additional subjects, showed that this specific allele on D18S63, which lies within an intron on the TGFB-induced factor (TGIF) gene, is strongly associated (P-value=0.0005) with psychosis. Eleven additional SNP markers, spanning five genes in the region, were analyzed in the combined sample from the CVCR. Only the four SNPs within the TGIF gene were in strong linkage disequilibrium with D18S63 (D'=1.00). A specific haplotype for all five markers within the TGIF gene showed evidence of association (P-value=0.011) to psychosis. A second, distinct haplotype, containing a newly identified nonsynonymous polymorphism in exon 5 of the TGIF gene, showed a nonsignificant trend towards association to psychosis (P-value=0.077). TGIF is involved in neurodevelopment, neuron survival and controls the expression of dopamine receptors. Altogether, our results point to the possible involvement of TGIF in the pathophysiology of psychotic disorders in the CVCR population.
精神分裂症（SC）和双相情感障碍（BP）有许多共同的临床特征，其中包括精神病性症状。我们之前在来自哥斯达黎加中央山谷（CVCR）人群的样本中，在18号染色体短臂上鉴定出一个与精神病性症状相关的假定基因位点。本研究使用新收集的CVCR样本，重复验证了与18p11.3上微卫星标记D18S63的特定等位基因的关联。对两个样本以及其他受试者的综合分析表明，位于TGFB诱导因子（TGIF）基因内含子内的D18S63上的这个特定等位基因与精神病性症状密切相关（P值 = 0.0005）。在CVCR的合并样本中分析了另外11个单核苷酸多态性（SNP）标记，这些标记跨越该区域的五个基因。只有TGIF基因内的四个SNP与D18S63处于强连锁不平衡状态（D' = 1.00）。TGIF基因内所有五个标记的一个特定单倍型显示出与精神病性症状相关的证据（P值 = 0.011）。第二个不同的单倍型，包含TGIF基因外显子5中一个新发现的非同义多态性，显示出与精神病性症状相关的非显著趋势（P值 = 0.077）。TGIF参与神经发育、神经元存活并控制多巴胺受体的表达。总之，我们的结果表明TGIF可能参与了CVCR人群中精神病性障碍的病理生理过程。
