Sequence variants of interleukin 6 (IL-6) are significantly associated with a decreased risk of late-onset Alzheimer's disease.

Shih-Yuan Chen,Li-Li Wen,Ping-Keung Yip,Jen-Hau Chen,Yen-Ching Chen,Yu Sun,Yi-Min Chu,Liang-Chuan Lai,Ta-Fu Chen

doi:10.1186/1742-2094-9-21

Abstract

BackgroundInterleukin 6 (IL-6) has been related to beta-amyloid aggregation and the appearance of hyperphosphorylated tau in Alzheimer's disease (AD) brain. However, previous studies relating IL-6 genetic polymorphisms to AD included few and unrepresentative single nucleotide polymorphisms (SNPs) and the results were inconsistent.MethodsThis is a case-control study. A total of 266 patients with AD, aged≧65, were recruited from three hospitals in Taiwan (2007-2010). Controls (n = 444) were recruited from routine health checkups and volunteers of the hospital during the same period of time. Three common IL-6 haplotype-tagging SNPs were selected to assess the association between IL-6 polymorphisms and the risk of late-onset AD (LOAD).ResultsVariant carriers of IL-6 rs1800796 and rs1524107 were significantly associated with a reduced risk of LOAD [(GG + GC vs. CC): adjusted odds ratio (AOR) = 0.64 and (CC + CT vs. TT): AOR = 0.60, respectively]. Haplotype CAT was associated with a decreased risk of LOAD (0 and 1 copy vs. 2 copies: AOR = 0.65, 95% CI = 0.44-0.95). These associations remained significant in ApoE e4 non-carriers only. Hypertension significantly modified the association between rs2069837 polymorphisms and the risk of LOAD (pinteraction = 0.03).ConclusionsIL-6 polymorphisms are associated with reduced risk of LOAD, especially in ApoE e4 non-carriers. This study identified genetic markers for predicting LOAD in ApoE e4 non-carriers.

Highlights

Interleukin 6 (IL-6) has been related to beta-amyloid aggregation and the appearance of hyperphosphorylated tau in Alzheimer’s disease (AD) brain
Because Apolipoprotein E (ApoE) e4 status and some vascular risk factors [e.g., hypertension, hyperlipidemia, and type 2 diabetes mellitus (DM)] may affect the pathogenesis of dementia [16,17,18], this study further explored the effect of modification by these factors
We found that a variant of single nucleotide polymorphisms (SNPs) rs1800796 is significantly associated with decreased risk of late-onset AD (LOAD), which is consistent with the findings from a Chinese study [12]

Summary

Introduction

Interleukin 6 (IL-6) has been related to beta-amyloid aggregation and the appearance of hyperphosphorylated tau in Alzheimer’s disease (AD) brain. Previous studies relating IL-6 genetic polymorphisms to AD included few and unrepresentative single nucleotide polymorphisms (SNPs) and the results were inconsistent. Dementia is a neurodegenerative disease characterized by decline or loss in cognitive function. Alzheimer’s disease (AD) is the most common cause of dementia. In the United States in 2006, AD was the fifth leading cause of death in the elderly (age 65 or older) [1]. In Taiwan, the prevalence of dementia is around 1.7-4.3% among the elderly [2] and the number of dementia patients keeps increasing. Dementia has become an important health issue in aging populations. Interleukin-6 (IL-6), an inflammatory cytokine, plays an important role in the development and differentiation

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Conclusion