title: Association of microRNA biogenesis pathway gene variants and alcohol dependence risk.
abstract: Alcohol dependence (AD) is a neuropsychiatric disorder to which both genetic and environmental factors contribute. Especially, multiple genetic factors are promising to explain the etiology of AD. microRNAs (miRNAs) are members of a family of noncoding small RNAs, which are thought to be responsible for the altered gene expression in neuropsychiatric disorders. We hypothesized that single nucleotide polymorphisms (SNPs) in the miRNA biogenesis pathway may result in dysregulation of miRNA levels inside the cell. The aim of this study was to test an association between miRNA biogenesis gene variants and AD risk. Real-time polymerase chain reaction genotyping experiment was conducted on DNA samples from 123 alcohol-dependent patients and 135 healthy controls. We found that AGO1 rs595961 (χ(2) = 9.066, p = 0.003; odds ratio [OR] = 0.459, 95% confidence interval [CI]: 0.275-0.768) and AGO2 rs4961280 (χ(2) = 4.111, p = 0.043; OR = 0.590, 95% CI: 0.353-0.986) G alleles have significantly altered the risk for AD, and also there is a significant association of GEMIN4 rs910924 (χ(2) = 5.291, p = 0.021; OR = 1.913, 95% CI: 1.094-3.344) T allele with the risk for AD. We also found statistically significant difference in AGO1 rs595961 (χ(2) = 11.139, p = 0.001) and DGCR8 rs1640299 (χ(2) = 13.001, p = 0.002) genotype frequencies between case-control groups. This is the first study to investigate the effects of SNPs in the miRNA biogenesis pathway on AD risk. In conclusion, we identified a significant association of miRNA biogenesis genes with altered AD risk, and these results could be a guide to research on the role of miRNAs in AD in the future.
authors.affiliation: 1 Department of Medical Biology and Genetics, Mersin University , Mersin, Turkey .
authors.forename: Huseyin
authors.initials: H
authors.lastname: Gedik
authors.forename: Mehmet Emin
authors.initials: ME
authors.lastname: Erdal
authors.forename: Senay Gorucu
authors.initials: SG
authors.lastname: Yilmaz
authors.forename: Cem
authors.initials: C
authors.lastname: Sengul
authors.forename: Ceyhan Balci
authors.initials: CB
authors.lastname: Sengul
authors.forename: Hasan
authors.initials: H
authors.lastname: Herken
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D060565:Argonaute Proteins / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics*; D055541:DEAD Box Protein 20 / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics; D039642:Eukaryotic Initiation Factors / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D028884:Karyopherins / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult; D020931:ran GTP-Binding Protein / Q000235:genetics
chemical_list: C115848:AGO1 protein, human; C466422:AGO2 protein, human; D060565:Argonaute Proteins; C474043:DGCR8 protein, human; D039642:Eukaryotic Initiation Factors; D028884:Karyopherins; D035683:MicroRNAs; C120587:RAN protein, human; D016601:RNA-Binding Proteins; C446511:XPO5 protein, human; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D020931:ran GTP-Binding Protein