Analysis of Association of Genetic Markers in the LUZP2 and FBXO40 Genes with the Normal Variability in Cognitive Performance in the Elderly.

Vadim Stepanov,Andrey Marusin,Anna Bocharova,Kseniya Vagaitseva,Valentina Markova,Oksana Makeeva,Larisa Minaycheva

doi:10.1155/2018/2686045

Abstract

Cognitive performance is an important endophenotype for various neurodegenerative and neuropsychiatric traits. In the present study two genetic variants in the leucine-zipper protein (LUZP2) and the F-box 40 protein (FBXO40) genes, previously reported to be genome-wide significant for Alzheimer's diseases and schizophrenia, were examined for an association with cognitive abilities in normal elderly from the Russian population. Rs1021261 in the LUZP2 and rs3772130 in the FBXO40 were genotyped by multiplex PCR and MALDI-TOF mass spectrometry in a sample of 708 normal elderly subjects tested for cognitive performance using the Montreal Cognitive Assessment (MoCA). Association of genetic variability with the MoCA scores was estimated by parametric and nonparametric analysis of variance and by the frequency comparison between upper and lower quartiles of MoCA distribution. Significantly higher frequency of “TT” genotype of rs1021261 in the LUZP2 gene as well as “A” allele and “AA” genotype of rs3772130 in the FBXO40 gene was found in a subsample of individuals with the MoCA score less than 20 comparing to the fourth quartile's subsample (MoCA > 25). The data of the present study suggests that genetic variability in the LUZP2 and FBXO40 loci associated with neurodegenerative and neuropsychiatric diseases is also contributed to the normal variability in cognitive performance in the elderly.

Highlights

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
This study aimed to examine whether the rs1021261 in the leucine-zipper protein 2 (LUZP2) gene and rs3772130 in the FBXO40 gene are associated with cognitive performance in the normal elderly population
Alleles and genotypes frequency of polymorphic variants in the LUZP2 and FBXO40 genes in a sample of 708 elderly subjects from the Russian population as well as in the first (MoCA < 20) and the fourth (MoCA > 25) quartiles of Montreal Cognitive Assessment (MoCA) scores distribution are presented in the Table 2

Summary

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. 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 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].

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