AKR1A1 variant associated with schizophrenia causes exon skipping, leading to loss of enzymatic activity

Highlights

Introduction

The accumulation of GlucA might be related to drug-resistant schizophrenia, since GlucA is known to promote drug excretion by forming conjugates with drugs. However, little is known about the molecular mechanisms underlying GlucA accumulation in patients with schizophrenia.

AKR1A1 is an approximately 40 kDa monomeric oxidoreductase, which is known to catalyze the reduction of GlucA. It can be assumed that AKR1A1 dysfunction leads accumulation of GlucA. Here, we aimed to explore genetic defects in AKR1A1 in patients with schizophrenia and identify the molecular mechanisms that cause the accumulation of GlucA.

Results

The AKR1A1 sequence was analyzed in patients with schizophrenia and control subjects, and 28 variants containing 4 novel variants were identified (Fig.1). Among them, four variants were found in the coding region. In particular, the c.753G>A variant was identified in 14 cases in the schizophrenia patient group and 5 subjects in the healthy group, and the c.264delC variant was observed in only one patient with schizophrenia.

Frontiers in Genetics

10.3389/fgene.2021.762999

AKR1A1 Variant Associated With Schizophrenia Causes Exon Skipping, Leading to Loss of Enzymatic Activity

6-Dec-2021