مفهوم پلی مورفیسم ژن IL-33 در بیماران چینی مبتلا به بیماری آلزایمر

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.

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 and Di Bona et al., 2009; Vasto et al., 2008 and 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.