Evaluation of Six SNPs of MicroRNA Machinery Genes and Risk of Schizophrenia
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Evaluation of Six SNPs of MicroRNA Machinery Genes and Risk of Schizophrenia Yi Zhou & Jun Wang & Xiaojun Lu & Xingbo Song & Yuanxin Ye & Juan Zhou & Binwu Ying & Lanlan Wang
Received: 19 July 2012 / Accepted: 10 September 2012 / Published online: 27 September 2012 # Springer Science+Business Media, LLC 2012
Abstract MicroRNAs (miRNAs) are small regulatory RNAs that modulate the expression of approximately half of all human genes. Small changes in miRNA expression have been associated with several psychiatric and neurological disorders, but whether the polymorphisms in genes involved in the processing of miRNAs into maturity influence the susceptibility of a person to schizophrenia (SZ) has not yet been elucidated. In this study, we investigated the association between SZ risk and single-nucleotide polymorphisms (SNPs) in microRNA machinery genes. We assessed the associations between SZ as a risk and six potentially functional SNPs from five miRNA processing genes (DROSHA, DGCR8, DICER, AGO1, and GEMIN4) in a case-control study of 256 Chinese SZ patients and 252 frequency-matched (age, gender, and ethnicity) controls. All the SNPs (rs10719, rs3757, rs3742330, rs636832, rs7813, and rs3744741) were genotyped by high resolution melting method. We found that two SNPs in the DGCR8 and DICER gene were significantly associated with the altered SZ risk. The genotype or allele frequency of rs3742330 in DICER was significantly different in patients and controls. Moreover, the recessive model of rs3757 in DGCR8 (AA vs. GA/GG) exhibited a significantly increased risk with an odds ratio Electronic supplementary material The online version of this article (doi:10.1007/s12031-012-9887-1) contains supplementary material, which is available to authorized users. Yi Zhou and Jun Wang have contributed equally to this work. Y. Zhou : J. Wang : X. Lu : X. Song : Y. Ye : J. Zhou : B. Ying (*) : L. Wang (*) Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, People’s Republic of China e-mail: [email protected] e-mail: [email protected]
(OR) of 3.73 [95 % confidence interval (CI), 1.03–13.52, P00.032]; the dominant model of rs3742330 in DICER (AA vs. AG/GG) exhibited a significantly increased risk with OR of 1.49 (95 % CI, 1.04–2.13; P00.028). Other SNPs and the haplotype of GEMIN4 (rs3744741 and rs7813) did not show any association with SZ. Our results suggested that the specific genetic variants in microRNA machinery genes may affect SZ susceptibility. Keywords MicroRNA . Polymorphism . Schizophrenia
Introduction Schizophrenia (SZ) is a debilitating mental disorder affecting approximately 1 % of the population worldwide. As one of the most expensive medical illness, SZ represents a serious burden on the health care system (Freedman 2003). Despite the fact that SZ is increasingly being understood as a neurodevelopmental disorder, the mechanism underlying the disease process has yet to be elucidated. MicroRNAs (miRNAs) are a group of small noncoding RNA molecules that individually regula
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