GRIK4 Polymorphism and its Association with Antidepressant Response in Depressed Patients: A Meta-Analysis

Abstract

Aim This study aimed to evaluate the relationship between a human GRIK4 gene polymorphism (rs1954787) and responsiveness to antidepressant treatment in depressed patients. Methods A meta-analysis was carried out on five studies. Pooled odds ratios (ORs), 95% CIs and a χ2 test measuring heterogeneity were calculated. A test of publication bias was also conducted. Results Alleles and genotypes from a total of 2169 depressed patients were analyzed. The results showed that the C allele appeared more frequently than the T allele in responders to treatment (OR: 1.22; 95% CI: 1.035–1.445; z = 2.36; p = 0.018). Similarly, CC homozygotes were more likely than TT homozygotes to respond to treatment (OR: 1.45; 95% CI: 1.107–1.913; z = 2.69; p = 0.007). No evidence of publication bias was detected. Conclusion Subjects possessing the C allele or CC genotype of the GRIK4 polymorphism rs1954787 are more likely to respond to antidepressant treatment relative to subjects harboring the T allele and TT genotype. Additional replication of this result is required before this association can be considered definitive, after which it may become possible to employ this marker in conjunction with other known predictors in order to anticipate the outcomes of treatment with antidepressant medications.

Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness

“…Consequently, the burden of mental disorders, especially depressive disorders, may be higher in African Americans [62]. If the association between genotype at rs1954787 and variable response to antidepressants becomes strongly definitive, this marker may be employed in conjunction with other known predictors to anticipate the outcome of treatments with antidepressants [63] considering the fact that more than 80% patients with African ancestry may be less likely to respond to antidepressants.…”

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

“…SSRIs) treatment response accounts for genetic factors, progress in uncovering the particular genetic polymorphisms has been slow [112]. As described in Table 1, candidate gene studies have pointed to a number of genes and SNPs that may influence antidepressant treatment outcomes [6, 7, 8-10, 26, 27, 54], including polymorphisms within the COMT [8,30], HTR2A [54,86,121], HTR1A [26], CNR1 [26], SLC6A4 [9], NPY [6], MAOA [27,30], IL1B [7,30], GRIK4 [64], BDNF [30,86], GNB3 [30], FKBP5 [86], CYP2D6 [31,121], CYP2C19 [31,121], and ABCB1 [12,86] genes (Table 1). For example, a negative influence of a higher activity COMT 158 val/val genotype on antidepressant treatment response was shown [].…”

“…Encodes a beta subunit of the G protein beta family of G proteins (guanine nucleotide-binding proteins) that help to integrate signals between receptor and effector proteins [121] GNB3 C825T polymorphism influences the efficacy of antidepressants in the treatment of MDD [64,88,89,101, 166]…”

“…Encodes serine-threonine kinase, a protein belonging to the glycogen synthase kinase subfamily that are involved in energy metabolism and neuronal cell development [90] GSK3B genetic variants may underlie therapeutic response to lithium [64,73] FYN gene polymorphism rs3730353 was associated with prophylactic response to lithium in bipolar patients [113] Circadian clock genes TIMELESS Timeless circadian clock PER3 Period circadian clock 3 CLOCK Circadian locomotor output cycle kaput ARNTL Aryl hydrocarbon receptor nuclear translocator-like TIMELESS, PER3, CLOCK and ARNTL are members of the Period family of genes mainly involved in the control of circadian pattern. They also control cell survival after damage or stress, locomotor activity, metabolism and behavior [90] Polymorphism in the circadian clock genes may be associated with lithium treatment and prophylactic response in bipolar illness [97] TPH1 Tryptophan hydroxylase-1…”

Isothermal-based DNA biosensors for application in pharmacogenetics

“…The trait was corroborated by a meta-analysis 2014 study, which concluded that subjects possessing the C allele or CC genotype of the GRIK4 polymorphism rs1954787 are more likely to respond to antidepressant treatment relative to subjects harboring the T allele and TT genotype (46).…”