The −1082G/A polymorphism in IL-10 gene is associated with risk of Alzheimer's disease: A meta-analysis
Introduction
Alzheimer's disease is the major cause of cognitive deterioration in the elderly and presents a substantial public health problem [1], [2], [3]. Its major characteristics include progressive synapse and neuronal loss, formation of neuritic plaques and neurofibrillary tangles [1], [4]. There are growing evidences to suggest that inflammatory process play a crucial role in the pathogenesis of AD [5]. Many inflammatory factors have been detected by pathological studies [6]. Multiple cytokines such as IL-6, TNF-α, IL-1β are overexpressed in activated microglia surrounding plaques in AD [7]. In addition, evidence suggests that the risk of AD is associated with genetic variants in inflammatory mediators, such as IL-1β [8], IL-6 [9], TNF-α [10] and IL-10 [11]. Genetic variants in these genes may affect biological activity by transcription, translation and secretion.
IL-10, a main anti-inflammatory cytokine, has been suggested to play an important role in neuronal homeostasis and cell survival [12]. It promotes neuronal and glial survival and downregulates the expression of pro-inflammatory cytokine genes through activation and/or induction of transcription factors [13]. IL-10-positive cells around beta plaques are increased significantly with age in AD animal models [14]. The human IL-10 gene is located on chromosome 1q31–32 and consists of five exons [1]. The IL-10 promoter region is highly polymorphic and many polymorphisms have been identified, such as −1082G/A(rs1800896), −829C/T(rs1800871) and −592C/A (rs1800872) [1]. A number of studies have reported the associations between −1082G/A polymorphism in IL-10 gene and AD risk [1], [2], [4], [11], [13], [15], [16], [17], [18], [19], [20], [21], but the results were inconclusive. This polymorphism was suggested as a risk factor for AD in Italian population [21] and Chinese population [19], but not in German population [13]. This is partly due to the different genetic effects in different ethnic populations [22]. In addition, a small sample size may result in weak statistical power [22]. In order to derive a more precise conclusion, we performed a meta-analysis to pool all available results of the association between IL-10 −1082G/A polymorphism and AD risk. This is, to our knowledge, the first genetic meta-analysis conducted with respect to the association between the IL-10 polymorphism and AD risk.
Section snippets
Publication search
We carried out a search in Pubmed and Embase, covering all the papers published before 2010, with a combination of the following words: polymorphism or mutation or variant, and interleukin-10 or IL-10, and Alzheimer's disease (last search was updated on September 17th, 2010). We evaluated potentially relevant publications by examining their titles and abstracts and all studies matching the eligible criteria were retrieved. All languages were included. Studies included in the current
Study characteristics
Pubmed and Embase databases were comprehensively searched. There were 158 records relevant to our searching strategy. After screening the titles and abstracts, 18 eligible articles were identified. During the extraction of data, 5 articles were excluded, because they did not provide the usable data of −1082G/A polymorphism for OR calculation. Additionally, one case-control was excluded for data repeated with another study. Thus, a total of 12 case-control studies were identified which met our
Discussion
AD is the leading cause of cognitive deterioration in the elderly, and affects approximately 10% after age of 65 [6]. Accumulated evidences indicate that neruoinflammation and cytokines appear to play a critical role in the development of AD. IL-10, an important cytokine, has an anti-inflammatory role in the brain and may be involved in the pathogenesis of AD. Genetic studies showed that the −1082G/A polymorphism in the promoter region was associated with AD risk, and a number of studies have
Conflict of Interest
None declared.
Acknowledgements
This study was supported by grants #30470761, 30871117 from National Natural Science Foundation of China.
References (24)
- et al.
Neither sequence variation in the IL-10 gene promoter nor presence of IL-10 protein in the cerebral cortex is associated with Alzheimer's disease
Neurosci Lett
(2006) - et al.
Association of polymorphism of DNA repair gene XRCC1 with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese
J Neurol Sci
(2010) - et al.
Inflammation and Alzheimer's disease
Neurobiol Aging
(2000) - et al.
The role of inflammation in Alzheimer's disease
Int J Biochem Cell Biol
(2005) - et al.
Association between the interleukin-1beta polymorphisms and Alzheimer's disease: a systematic review and meta-analysis
Brain Res Rev
(2008) - et al.
The interleukin-6 gene -572C/G promoter polymorphism modifies Alzheimer's risk in APOE epsilon 4 carriers
Neurosci Lett
(2010) - et al.
Promoter haplotypes of interleukin-10 gene and sporadic Alzheimer's disease
Neurosci Lett
(2004) - et al.
Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology
Brain Res
(2001) - et al.
Association of IL10 promoter polymorphism in Italian Alzheimer's disease
Neurosci Lett
(2007) - et al.
The association between promoter polymorphism of the interleukin-10 gene and Alzheimer's disease
Neurobiol Aging
(2005)
Lack of association of interleukin-10 promoter region polymorphisms with Alzheimer's disease
Neurosci Lett
The MTHFR C677T polymorphism contributes to an increased risk for vascular dementia: a meta-analysis
J Neurol Sci
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- 1
Contributed equally to this study.