title: A genetic variant in miRNA binding site of glutamate receptor 4, metabotropic (GRM4) is associated with increased risk of major depressive disorder.
abstract: Glutamate receptor 4, metabotropic (GRM4) expression is increased in the brain of patients with depression. The poorly conserved miR-1202 is downregulated in depression and is negatively correlated with GRM4. A variation located at the 3' UTR of the GRM4 gene may influence the interaction between miR-1202 and GRM4. The aim of this study was to determine the possible association between GRM4 3' UTR variant (rs2229901) and major depressive disorder (MDD).
  
  
  
  A total of 500 subjects comprising 250 patients with MDD and 250 healthy controls were included in our study. The single nucleotide polymorphism rs2229901 was genotyped using PCR-RFLP method. Allele and genotype frequencies were compared between the two groups using chi-square test and logistic regression models. The impact of rs2229901 on GRM4/miR-1202 hybrid stability and local GRM4-3' UTR secondary structure were assessed using RNAsnp program.
  
  
  
  Genotype and allele frequency of rs2229901were significantly different in patients with MDD comparing to the control group (p=0.018 and p=0.007, respectively). The G-allele was more prevalent among patients with MDD. The rs2229901 variant was predicted to be structure-disruptive.
  
  
  
  The relatively small sample size and lack of functional experiments are the major limitations of this study.
  
  
  
  Our results suggest that rs2229901 is associated with MDD risk. This variant probably impacts the interaction between GRM4 and miR-1202. Functional studies are needed to clarify the possible mechanisms by which rs2229901 influences MDD risk.
authors: Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran.
authors: Tahereh
authors: T
authors: Dadkhah
authors: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Simin
authors: S
authors: Rahimi-Aliabadi
authors: Noncommunicable Diseases Research Center, Fasa University ofMedical Sciences, Fasa, Iran.
authors: Javad
authors: J
authors: Jamshidi
authors: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Hamid
authors: H
authors: Ghaedi
authors: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Shaghyegh
authors: S
authors: Taghavi
authors: Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors: Parasto
authors: P
authors: Shokraeian
authors: Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran.
authors: Haleh
authors: H
authors: Akhavan-Niaki
authors: Department of Neurology, School of Medicine, Imam Khomeini Hospital and Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
authors: Abbas
authors: A
authors: Tafakhori
authors: Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors: Mina
authors: M
authors: Ohadi
authors: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: darvish_mg@sbmu.ac.ir.
authors: Hossein
authors: H
authors: Darvish
mesh_terms: D000328:Adult; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism; D012306:Risk
chemical_list: D035683:MicroRNAs; D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4
keywords: Depression; GRM4; MiR-1202; Single nucleotide polymorphism