Abstract

BackgroundMolybdenum cofactor sulfurase (MOCOS) is an enzyme participating in purine metabolism. The aim of current study was to evaluate the role of a single nucleotide polymorphism (SNP) in the coding gene (rs594445) in mood disorders and methamphetamine addiction.MethodsThis SNP was genotyped in 200 persons with methamphetamine addiction, 85 patients with bipolar disorder 1 (BP1), 78 patients with BP2, 33 patients with major depressive disorder (MDD) and 200 age-/sex-matched normal subjects using the tetra-primer amplification-refractory mutation system (ARMS)-PCR technique.ResultsThe rs594445 was associated with methamphetamine addiction in co-dominant model [A/A vs C/C: OR (95% CI) = 0.466 (0.252–0.864), P-value = 0.014; C/A vs C/C: OR (95% CI) = 0.641 (0.418–0.981), P-value = 0.04]. This SNP was also associated with this trait in dominant model [OR (95% CI) = 0.591 (0.398–0.879), P-value = 0.009]. The A allele of rs594445 had a protective role against methamphetamine addiction [A vs C: OR (95% CI) = 0.645 (0.48–0.866), P-value = 0.004]. The rs594445 was associated with BP1 in co-dominant model [C/A vs C/C: OR (95% CI) = 0.423 (0.230–0.778), P-value = 0.005]. However, the associations were insignificant in other inheritance models.ConclusionFinally, there were no significant associations between the mentioned SNP and risk of BP2 or MDD in any inheritance model. The present project highlights the role rs594445 in two psychiatric conditions and implies the presence of common genetic factors for these disorders.

Highlights

  • Molybdenum cofactor sulfurase (MOCOS) being encoded by the MOCOS gene transfers a sulfur atom to the molybdenum cofactor of xanthine dehydrogenase (XDH) and aldehyde oxidase (AOX1) and activates these enzymes (Ichida et al, 2001; Taheri et al, 2020)

  • Based on the proposed role for MOCOS in neurodevelopment and neurotransmission (Feron et al, 2016), we aimed to identify its role in two psychiatric conditions namely mood disorders and methamphetamine addiction

  • The rs594445 was associated with methamphetamine addiction in co-dominant model [A/A vs C/C: Odds ratios (OR) = 0.466 (0.252–0.864], P-value = 0.014; C/A vs C/C: OR = 0.641 (0.418–0.981), P-value = 0.04]

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Summary

Introduction

Molybdenum cofactor sulfurase (MOCOS) being encoded by the MOCOS gene transfers a sulfur atom to the molybdenum cofactor of xanthine dehydrogenase (XDH) and aldehyde oxidase (AOX1) and activates these enzymes (Ichida et al, 2001; Taheri et al, 2020). Functional studies have shown that dysregulation in expression of this gene leads to synaptic flaws as well as hypersensitivity to oxidative stress (Feron et al, 2016). MOCOS has been shown to be expressed in several regions of the developing and adult human brain. Studies in mouse brain tissues have verified its expression in the hippocampus, cortex, cerebellum and brainstem (Feron et al, 2016). The aim of current study was to evaluate the role of a single nucleotide polymorphism (SNP) in the coding gene (rs594445) in mood disorders and methamphetamine addiction

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