Research article

Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population

Fuquan Zhang^1,3 , Yong Xu¹ , Pozi Liu¹ , Hua Fan² , Xuezhu Huang¹ , Gaoxiang Sun¹ , Yuqing Song³ and Pak C Sham³

¹  Institute of Neurological disorders, Tsinghua University, Department of Psychiatry, Yuquan Hospital, Tsinghua University, Bejing, 100049, PR China

²  Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Bejing, PR China

³  Department of Psychiatry, University of Hong Kong, Hong Kong, PR China

author email corresponding author email

BMC Medical Genetics 2008, 9:119doi:10.1186/1471-2350-9-119

Published:	30 December 2008

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.