Association and Interaction Effects of Interleukin-12 Related Genes and Physical Activity on Cognitive Aging in Old Adults in the Taiwanese Population.

Eugene Lin,Albert C Yang,Shih-Jen Tsai,Yu-Li Liu,Po-Hsiu Kuo

doi:10.3389/fneur.2019.01065

Abstract

Evidence suggests that the neuro-inflammation mechanisms associated with interleukin-12 (IL-12) may be linked to Alzheimer's diseases and cognitive aging. In this study, we speculate that single nucleotide polymorphisms (SNPs) in IL-12-associated genes, such as IL12A, IL12B, IL12RB1, and IL12RB2 genes, could be associated with cognitive aging individually and/or via complicated interactions in the elder Taiwanese population. There were totally 3,730 Taiwanese individuals with age ≥60 years from the Taiwan Biobank. Mini-Mental State Examination (MMSE) was analyzed for all participants. We employed MMSE scores to assess cognitive functions. Our analysis revealed that the IL12A gene (including rs116910715, rs78902931, and rs78569420), the IL12B gene (including rs730691), and the IL12RB2 gene (including rs3790558, rs4655538, rs75699623, and rs1874396) were associated with cognitive aging. Among these SNPs, the association with the IL12RB2 rs3790558 SNP remained significant after performing Bonferroni correction (P = 6.87 × 10−4). Additionally, we found that interactions between the IL12A and IL12RB2 genes influenced cognitive aging (P = 0.022). Finally, we pinpointed the effects of interactions between IL12A, IL12B, and IL12RB2 with physical activity (P < 0.001, = 0.002, and < 0.001, respectively). Our study suggests that the IL-12-associated genes may contribute to susceptibility to cognitive aging independently as well as through gene-gene and gene-physical activity interactions.

Highlights

Interleukin-12 (IL-12) is a pro-inflammatory cytokine that builds a key link between adaptive immunity and innate resistance [1]
We explored the associations between cognitive aging and four IL-12 related genes, namely the interleukin 12A (IL12A), interleukin 12B (IL12B), interleukin 12 receptor subunit beta 1 (IL12RB1), and interleukin 12 receptor subunit beta 2 (IL12RB2) genes
The present study is the first to date to identify whether the major impacts of 35 tag single nucleotide polymorphisms (SNPs) within four IL-12-associated genes, namely the IL12A, IL12B, IL12RB1, and IL12RB2 genes, are significantly linked to the risk of cognitive aging individually and via gene-gene and gene-physical activity interactions in elder Taiwanese subjects

Summary

Introduction

Interleukin-12 (IL-12) is a pro-inflammatory cytokine that builds a key link between adaptive immunity and innate resistance [1]. There is growing evidence that IL-12 is regulated in neuro-inflammatory processes associated with neurodegenerative disorders such as Alzheimer’s disease (AD) and mild cognitive impairment [2, 3]. A subtype of mild cognitive impairment (that is, non-amnestic multiple domain) was associated with higher levels of IL-12 and IL-12β [5]. It has been suggested that IL-12β is involved in affecting Mini-Mental State Examination (MMSE) test scores and gray-matter volumes of lateral prefrontal cortex and hippocampus in older adults [8]. It has been reported that elderly persons with inadequate physical activity showed higher levels of IL-12β, smaller gray-matter volumes, and more cognitive decline than active elderly persons, suggesting probable gene-physical activity interactions [8]

Methods

Results

Conclusion