Elsevier

Neurobiology of Aging

Volume 33, Issue 5, May 2012, Pages 1014.e11-1014.e14
Neurobiology of Aging

Genetic reports abstract
Implication of IL-33 gene polymorphism in Chinese patients with Alzheimer's disease

https://doi.org/10.1016/j.neurobiolaging.2010.07.003Get rights and content

Abstract

Interleukin-33 (IL-33), a newly described member of the IL-1 family, is located on chromosome 9p24, a chromosomal region of interest in Alzheimer's disease (AD) defined by many genome-wide studies. Three intronic rs1157505, rs11792633, and rs7044343 single nucleotide polymorphisms (SNPs) within IL-33 have recently been reported to be associated with risk of AD in Caucasian populations. In order to assess the involvement of the IL-33 polymorphisms in the risk of developing late onset AD (LOAD), we analyzed the genotype and allele distributions of these 3 polymorphisms in 704 Han Chinese subjects. The minor alleles of the rs11792633 polymorphism within IL-33 was significantly associated with a reduced risk of LOAD (odds ratio [OR] = 0.73, p = 0.005). Furthermore, rs11792633 polymorphism was still strongly associated with LOAD (dominant model: OR = 0.67, p = 0.015; recessive model: OR 0.57, p = 0.021; additive model: OR = 0.71, p = 0.004) after adjusting for age, gender, and the apolipoprotein E (APOE) ε4 status. Our results support the evidence that genetic variants of IL-33 affect susceptibility to LOAD in Han Chinese.

Introduction

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, with a prevalence of over 35 million worldwide (Querfurth and LaFerla, 2010). Considerable evidence gained over the past decade has supported that the risk of AD is substantially influenced by genetic variation in the inflammatory agents, including interleukin (IL)-1, IL-1β, IL-6, IL-18, tumor necrosis factor α (TNF-α) (Di Bona et al., 2008, Di Bona et al., 2009; Vasto et al., 2008, Yu et al., 2009). Recently, 3 intronic rs1157505, rs11792633, and rs7044343 single nucleotide polymorphisms (SNPs) within IL-33 have been reported to be associated with risk of AD in 3 independent case-control studies and a prospective population-based study from the Caucasian populations (Chapuis et al., 2009). Furthermore, functional studies have shown that these polymorphisms were associated with less cerebral amyloid angiopathy (CAA) in the brain of non-apolipoprotein E (APOE) ε4 AD cases, ultimately leading to a specific decrease in secretion of the amyloid-β40 (Aβ40) peptide. As variants and their frequencies of chromosome IL-33 in various ethnic groups might be different, replication is needed to confirm the potential effects of chromosome IL-33 in other groups. To date, genetic variability of IL-33 has not been examined among Asians. To address this question, we conducted the first genetic association study on IL-33 in an Asian (Chinese) cohort of AD and controls.

Section snippets

Subjects

Our study comprised of 322 sporadic late onset AD (LOAD) (age at onset ≥65 years) patients (women 179; mean age: 76.53 ± 5.64 years) and 382 healthy controls (women 207; mean age: 75.71 ± 4.82 years) matched for gender and age. All the above subjects were Northern Han Chinese in origin. The patients were recruited from the Department of Neurology of the Qingdao Municipal Hospital, and several other hospitals in Shandong Province. A clinical diagnosis of probable AD was established according to

Results

Because no rs1157505 polymorphism was detected in any of the 704 subjects, only the wild-type was present in this study. Allelic and genotype frequencies of rs11792633 and rs7044343 SNPs in LOAD patients and controls are reported in Table 1. Distributions of the IL-33 and APOE polymorphisms in both patients and controls did not deviate from those predicted by the Hardy-Weinberg equilibrium except for the rs7044343 polymorphism in control group (p = 0.045). For rs11792633, there were significant

Discussion

Here, we report for the first time the significant association of the rs11792633 SNP in IL-33 with a reduced risk of LOAD in a Han Chinese population. The minor alleles of rs11792633 and rs7044343 defined a 2-site protective haplotype. Our results were partially consistent with the results of Chapuis et al. (2009). In Chapuis et al.'s study, the minor allele frequencies of the intronic rs1157505, rs11792633, and rs7044343 SNPs within IL-33 in controls were 22.9%–25.0%, 31.6%–32.3%, and

Disclosure statement

The authors have no potential conflicts of interest to report.

An informed consent to participate in this study was obtained from each subject or from a guardian, and the protocol of this study was approved by the Ethical Committee of Qingdao Municipal Hospital.

Acknowledgements

This work was supported by grants from National Natural Science Foundation of China (30870884) and Shandong Provincial Outstanding Medical Academic Professional Program.

References (16)

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