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

作者：Dadkhah Tahereh; Rahimi Aliabadi Simin; Jamshidi Javad; Ghaedi Hamid; Taghavi Shaghyegh; Shokraeian Parasto; Akhavan Niaki Haleh; Tafakhori Abbas; Ohadi Mina; Darvish Hossein^*

来源：Journal of Affective Disorders, 2017, 208: 218-222.

DOI：10.1016/j.jad.2016.10.008

• Depression
• Single nucleotide polymorphism
• GRM4
• MiR-1202

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 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).
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 GRM4-3' UTR 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.

• 出版日期2017-1-15