title: Evaluation of six SNPs of MicroRNA machinery genes and risk of schizophrenia.
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 (OR) of 3.73 [95 % confidence interval (CI), 1.03-13.52, P = 0.032]; 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; P = 0.028). 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.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lu
authors.forename: Xingbo
authors.initials: X
authors.lastname: Song
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Ye
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D060565:Argonaute Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D053487:DEAD-box RNA Helicases / Q000235:genetics; D039642:Eukaryotic Initiation Factors / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
chemical_list: C115848:AGO1 protein, human; D060565:Argonaute Proteins; C474043:DGCR8 protein, human; D039642:Eukaryotic Initiation Factors; C406815:GEMIN4 protein, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D011506:Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases