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

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

Description

Interleukin 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. Methods This 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). Results Variant 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 ( p interaction = 0.03). Conclusions IL-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.

Sujets

• IL-6
• SNP
• Haplotype
• Alzheimer's disease
• Inflammation

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 12
• Langue: English

Extrait

Chenet al.Journal of Neuroinflammation2012,9:21 http://www.jneuroinflammation.com/content/9/1/21

JOURNAL OF NEUROINFLAMMATION

R E S E A R C HOpen Access Sequence variants of interleukin 6 (IL6) are significantly associated with a decreased risk of lateonset Alzheimer’s disease 1 23 1,45 67 ShihYuan Chen , TaFu Chen , LiangChuan Lai , JenHau Chen, Yu Sun , LiLi Wen , PingKeung Yip , 8,9 1,10,11* YiMin Chu and YenChing Chen

Abstract Background:Interleukin 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 relatingIL6genetic polymorphisms to AD included few and unrepresentative single nucleotide polymorphisms (SNPs) and the results were inconsistent. Methods:This 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 commonIL6haplotypetagging SNPs were selected to assess the association betweenIL6polymorphisms and the risk of lateonset AD (LOAD). Results:Variant carriers ofIL6rs1800796 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 inApoE e4noncarriers only. Hypertension significantly modified the association between rs2069837 polymorphisms and the risk of LOAD (p interaction = 0.03). Conclusions:IL6polymorphisms are associated with reduced risk of LOAD, especially inApoE e4noncarriers. This study identified genetic markers for predicting LOAD inApoE e4noncarriers. Keywords:IL6, SNP, Haplotype, Alzheimer?’?s disease, Inflammation

Background Dementia is a neurodegenerative disease characterized by decline or loss in cognitive function. Alzheimer’s dis ease (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. Therefore, 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

* Correspondence: [e-mail] 1 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Full list of author information is available at the end of the article

of neurons in both peripheral and central nervous sys tem [3]. IL6 promotes the activation of microglia [4] and then induces the synthesis of acute phase proteins [5] and phosphorylation of tau protein in neurons [6]. In AD brain, microglia and astrocytes are stimulated by IL6 and are recruited to release proinflammatory cyto kines and acutephase proteins, such as Creactive pro tein (CRP) [7]. Therefore, IL6 plays a pivotal role in brain inflammation that maybe important in AD pathogenesis. Previous studies relatingIL6polymorphisms to AD risk have been inconsistent. A Caucasian study found that the CC genotype ofIL6promoter SNP rs1800795 was significantly associated with an increased risk for AD [8]. However, this association has not been observed in other Caucasian studies [911]. In addition, the GG

© 2012 Chen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.