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A genetic variant in miRNA binding site of glutamate receptor 4, metabotropic (GRM4) is associated with increased risk of major depressive disorder.

J Affect Disord. 2017 Jan 15;208:218-222. Epub 2016 Oct 17
Tahereh Dadkhah 1 , Simin Rahimi-Aliabadi 2 , Javad Jamshidi 3 , Hamid Ghaedi 2 , Shaghyegh Taghavi 2 , Parasto Shokraeian 4 , Haleh Akhavan-Niaki 1 , Abbas Tafakhori 5 , Mina Ohadi 6 , Hossein Darvish 7
Tahereh Dadkhah 1 , Simin Rahimi-Aliabadi 2 , Javad Jamshidi 3 , Hamid Ghaedi 2 , Shaghyegh Taghavi 2 , Parasto Shokraeian 4 , Haleh Akhavan-Niaki 1 , Abbas Tafakhori 5 , Mina Ohadi 6 , Hossein Darvish 7
+ et al

[No authors listed]

Author information
  • 1 Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran.
  • 2 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 3 Noncommunicable Diseases Research Center, Fasa University ofMedical Sciences, Fasa, Iran.
  • 4 Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
  • 5 Department of Neurology, School of Medicine, Imam Khomeini Hospital and Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
  • 6 Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
  • 7 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: darvish_mg@sbmu.ac.ir.

摘要


BACKGROUND: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 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 duanyu3 variant (rs2229901) and major depressive disorder (MDD). METHODS: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 secondary structure were assessed using RNAsnp program. RESULTS: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. LIMITATIONS:The relatively small sample size and lack of functional experiments are the major limitations of this study. CONCLUSION: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.

KEYWORDS: Depression, GRM4, MiR-1202, Single nucleotide polymorphism