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

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Journal of Neuroinflammation (Impact Factor: 5.41). 01/2012; 9(1):21. DOI: 10.1186/1742-2094-9-21
Source: PubMed


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.
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).
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 (pinteraction = 0.03).
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.

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    • "12 ; Kalmady et al . , 2014 ) . Specifically , rs1800795 has been associated with reduced hippo - campal volume in both patients with schizophrenia and in healthy older adults , and rs1800796 and rs1524107 have been associated with reduced risk of late onset AD ; these IL - 6 genotypes are worth exploring in future studies ( Baune et al . , 2012 ; Chen et al . , 2012 ; Kalmady et al . , 2014 ) . A third potential mechanism could be greater overall morbidity , especially in terms of vascular and metabolic disease , which we may be capturing when looking at IL - 6 variability . Vascular disease risk factors such as diabetes , APOE gene variants , and metabolic syndrome components have all been associa"
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    ABSTRACT: We aimed to investigate if trajectory components (baseline level, slope, and variability) of peripheral interleukin-6 (IL-6) over time were related to cognitive impairment and smaller hippocampal volume and if hippocampal volume explained the associations between IL-6 and cognitive impairment. Multivariable regression models were used to test the association between IL-6 trajectory components with change in neuroimaging measures of the hippocampus and with cognitive impairment among 135 older adults (70-79 years at baseline) from the Healthy Brain Project over 14 years. IL-6 variability was positively associated with cognitive impairment (odds ratio [OR] = 5.86, 95% confidence interval [CI]: 1.24, 27.61) and with greater decrease per year of gray matter volume of the hippocampus (β = -0.008, standard error = 0.004, p = 0.03). After adjustment for hippocampal volume, the OR of cognitive impairment decreased for each unit of IL-6 variability and CIs widened (OR = 4.36, 95% CI: 0.67, 28.29). Neither baseline levels nor slopes of IL-6 were related to cognitive impairment or hippocampal volume. We believe this has potential clinical and public health implications by suggesting adults with stable levels of peripheral IL-6 may be better targets for intervention studies for slowing or preventing cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 07/2015; DOI:10.1016/j.neurobiolaging.2015.07.025 · 5.01 Impact Factor
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    • "IL-6-174 G/C (rs1800795) Bagli et al. 2000 Germany Caucasian 102 351 Bhojak et al. 2000 USA Caucasian 464 337 Pola et al. 2002 Italy Caucasian 124 134 Shibata et al. 2002 Japan Asian 128 83 Faltraco et al. 2003 Japan Caucasian 101 133 Licastro et al. 2003 Italy Caucasian 332 393 Arosio et al. 2004 Italy Caucasian 59 65 Capurso et al. 2004 Italy Caucasian 168 220 Depboylu et al. 2004 Germany Caucasian 113 108 Zhang et al. 2004 UK Caucasian 356 434 Koivisto et al. 2005 Finland Caucasian 65 542 Vural et al. 2009 Turkey Caucasian 101 138 Capurso et al. 2010 Italy Caucasian 149 298 Mansoori et al. 2010 India Asian 74 113 Combarros et al.* 2005 Spain Caucasian 234 197 Fontalba et al.* 2009 Spain Caucasian 239 165 Infante et al.* 2004 Spain Caucasian 232 201 Oijen et al. 2006 Netherlands Caucasian 483 4069 Paradowski et al. 2008 Poland Caucasian 51 36 Klimkowicz-Mrowiec et al.2010 Poland Caucasian 361 200 Papassotiropoulos et al. * 1999 UK Caucasian 102 351 Mateo et al. # 2005 Spain Caucasian 242 220 IL-6-572 C/G (rs1800796) Eriksson et al. 2011 USA Caucasian 1255 2363 He et al. 2010 China Asian 318 324 Nishimura et al. 2004 Japan Asian 172 163 Wang et al. 2010 China Asian 341 421 Chen et al.* 2012 Taiwan Mix 266 444 "
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    ABSTRACT: Associations between interleukin 6 (IL-6) polymorphisms and Alzheimer's disease (AD) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations for the relationship between IL-6-174 G/C and -572 C/G polymorphisms and risk for AD. Electronic searches for all publications in databases PubMed and EMBASE were conducted on the associations between IL-6 polymorphisms and risk for AD until January 2012. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. Twenty-seven studies were included with a total of 19,135 individuals, involving 6,632 AD patients and 12,503 controls. For IL-6-174 G/C polymorphism, the combined results showed significant differences in recessive model (CC vs. CG+GG: OR = 0.65, 95%CI = 0.52-0.82). As regards IL-6-572 C/G polymorphism, significant associations were shown in dominant model (CG+GG vs. CC: OR= 0.73, 95% CI = 0.62-0.86) and in additive model (GG vs. CC, OR= 0.66, 95% CI = 0.46-0.96). In conclusion, genotype CC of IL-6-174 G/C and genotype GG plus GC of IL-6-572 C/G could decrease the risk of AD.
    PLoS ONE 06/2012; 7(6):e37858. DOI:10.1371/journal.pone.0037858 · 3.23 Impact Factor
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