Association of ARRB1 polymorphisms with the risk of major depressive disorder and with treatment response to mirtazapine

Abstract

β-Arrestin 1 is known to be involved in the pathophysiology of major depressive disorder (MDD) and in the underlying mechanism of action of antidepressant therapies. After we screened 39 ARRB1 polymorphisms, we investigated the associations of seven ARRB1 single-nucleotide polymorphisms (SNPs) with the risk of MDD in 270 patients with MDD and 204 normal subjects, and with mirtazapine treatment response in patients with MDD. The genotype distributions of -132C>T and IVS1+85T>C showed significant deviations from Hardy-Weinberg equilibrium in patients with MDD but not in normal subjects. After four and 12 weeks of mirtazapine treatment, the proportion of haplotype 1 (ht1) carriers was significantly higher in remitters than in non-remitters after corrections for multiple comparisons (corrected p=0.006 and 0.014 at four and 12 weeks, respectively). After eight and 12 weeks of treatment, scores on the 21-item Hamilton Depression Rating Scale (HAMD21) were significantly lower in patients with MDD with ARRB1 ht1 than in those without ht1. Similarly, after 8 and 12 weeks of treatment, the percent reduction in HAMD21 scores was significantly higher in patients with MDD with ARRB1 ht1 than in those without ht1. The ARRB1 polymorphisms represent promising genetic markers for the prediction of treatment responses to mirtazapine.

Multivariate Imaging Genetics Study of MRI Gray Matter Volume and SNPs Reveals Biological Pathways Correlated with Brain Structural Differences in Attention Deficit Hyperactivity Disorder

“…The unexpected findings of pathways related to transmission and signaling in heart muscle [dilated and hypertrophic cardiomyopathy (HCM) and adrenergic signaling in cardiomyocytes], insulin secretion, estrogen signaling, and endocytosis likely occurred because many of the genes in those systems overlapped with those discussed above, including CACNA1C, CACNB4, ITGB6, ACE, ADCY9, ADRB2, AGAP1, ARRB1, CREB3L2, FKBP5, HSPA1L, TFRC , and VPS37C . Numerous studies have shown these genes are expressed in brain, responsible for neurogenesis ( 102 – 105 ), or associated with neuropsychiatric disorders ( 106 – 109 ).…”

Arrestin mutations: Some cause diseases, others promise cure

“…Polymorphism in the promoter region of the ARRB1 gene was found to be associated with the treatment outcome with antidepressant mirtazapine in Korean patients with major depressive disorder. 65 One haplotype, which includes SNPs in the promoter region and the first intron, was found to be associated with the remission status following several weeks of mirtazapine treatment. Two SNPs in ARRB2 , one in an intron and one in 3′-untranslated region (3′-UTR), were reported to be associated with the effects of antidepressant monotherapy in a group of mostly Caucasian patients with major depression.…”

Mirtazapine and Depressions

“…The adrenergic alpha 2a receptor-1291C/G polymorphism is associated with weight gain and treatment response to mirtazapine in patients with major depressive disorder (Lee et al 2009). Finally polymorphism of beta-arrestin (Lt1) influences downstream signaling of G-protein-coupled receptors and is associated with mirtazapine responses (Chang et al 2015).…”