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

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.