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

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.

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