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Received Oct 3, 2017; Accepted Mar 15, 2018
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1. Introduction
Cognitive decline with the age, both in the normal aging and in the pathological manifestations in form of dementia, is an important public health and social challenge. Individual variability of cognitive functions is an important endophenotype of many neurodegenerative, psychiatric, and mental diseases, such as schizophrenia (SZ) [1], Alzheimer’s diseases (AD) [2], bipolar disorder [3], and attention-deficit hyperactivity disorder [4]. Recent genome-wide association studies (GWAS) have revealed dozens of single nucleotide polymorphisms (SNPs) associated with a cognitive performance in SZ or AD patients, as well as in normal healthy subjects [5–10]. Some of genome-wide significant cognitive functions markers demonstrate an association with diseases as well, indicating overlapping genetic mechanisms underlying normal and pathological neurocognitive traits. Among genome-wide significant AD markers, revealed in the recent GWA studies, there are genetic variants in the leucine-zipper protein 2 (LUZP2) and the F-box 40 protein (FBXO40) genes.
LUZP2 gene on chromosome 11 encodes a leucine-zipper protein of unknown function, which is normally expressed only in the brain and the spinal cord. LUZP2 gene is deleted in some patients with Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome [11]. Polymorphic variants in this gene were reported to be associated with the late-onset Alzheimer’s disease [12], as well as with schizophrenia [13, 14], intelligence [15], and verbal memory [16]. Also a duplication which includes the LUZP2 gene was observed in AD patient [17]. Haplotypes around intronic rs1021261 in the LUZP2 gene were genome-wide significantly associated with the intelligence in an ancestrally homogeneous family sample of individuals with at least one child affected by attention-deficit hyperactivity disorder (ADHD) [15].
FBXO40 gene on chromosome 3 encodes a member of the F-box protein family which is characterized by an approximately 40-amino acid F-box motif. F-box 40 protein is substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that may function in myogenesis and in insulin growth factor (IGF) signaling in the brain and CNS. Potentially FXBO40 may be involved in neurodegenerative and neuropsychiatric diseases through alterations of the IGF-I neuronal...