Zhang Fuquan, Xu Yong, Liu Pozi, Fan Hua, Huang Xuezhu, Sun Gaoxiang, Song Yuqing, Sham Pak C
Institute of Neurological disorders, Tsinghua University, Department of Psychiatry, Yuquan Hospital, Tsinghua University, Bejing, 100049, PR China.
BMC Med Genet. 2008 Dec 30;9:119. doi: 10.1186/1471-2350-9-119.
The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes.
Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform.
There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10.
These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population.
与对照组相比，在精神分裂症患者中发现腺苷酸琥珀酸合成酶（ADSS）和共济失调毛细血管扩张症突变基因（ATM）的血液来源RNA水平分别下调和上调，并且ADSS和ATM是用于区分精神分裂症患者与正常对照的八个生物标志物基因之一。ADSS催化AMP合成的第一步，而ATM激酶在DNA双链断裂反应途径中作为关键信号转导分子。目前尚不清楚这些变化是否由这两个基因的突变或多态性引起。
对488例精神分裂症患者和516例对照的中国人群中ADSS基因的6个单核苷酸多态性（SNP）和ATM基因的3个SNP进行基因分型，以检查它们与精神分裂症（SZ）的关联。使用Sequenom平台进行基因分型。
病例组和对照组之间9个SNP的基因型、等位基因或单倍型分布没有显著差异。使用多因素降维（MDR）方法，我们发现ADSS基因中的rs3102460与ATM基因中的rs227061和rs664143之间的相互作用显示与SZ有显著关联。该模型的最大测试准确率为60.4%，最大交叉验证一致性为10中取10。
这些发现表明，ADSS和ATM基因多态性的联合作用可能使中国人群易患SZ。
