title: Interleukin-18 promoter polymorphisms and risk of late onset Alzheimer's disease.
abstract: Pro- and anti-inflammatory cytokines play an important role in Alzheimer's disease (AD), and common polymorphisms of genes controlling their production have been shown to be associated with the susceptibility to sporadic AD. Interleukin (IL)-18 is a potent pro-inflammatory cytokine of the IL-1 superfamily, and increasing evidences indicate a crucial role for it in the pathogenesis of AD. To clarify the role of IL-18 as a potential cause for AD susceptibility, we investigated the effect of two functional polymorphisms in IL-18 promoter: -607 C/A (rs1946518) and -137 G/C (rs187238) for the risk of sporadic late onset Alzheimer's disease (LOAD) in a Han Chinese population of 109 patients and 109 healthy controls matched for sex and age. All 218 subjects were also genotyped for the Apolipoprotein E (ApoE) polymorphisms. The results revealed that both -607 C allele and -137 G allele were associated with an increased risk of LOAD (odds ratios/OR=1.56, P=0.04, Power=0.96 and OR=1.85, P=0.03, Power=0.80, respectively), and these associations were influenced by the presence of ApoE epsilon4 alleles. Moreover, they showed a highly significant synergistical interaction with the ApoE epsilon4 allele (OR=5.70 and 4.64, respectively). Examination of the haplotypes identified the -607 C/-137 G haplotype to increase the risk of LOAD (OR=1.62, P=0.003, Power=0.97). These findings suggest that the functional polymorphisms in IL-18 promoter may be involved in the risk of developing sporadic LOAD in the Han Chinese population.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Affiliated Hospital of Qingdao University, Shandong Province, PR China.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Song
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Miao
authors.forename: Yan
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D020125:Mutation, Missense; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D020382:Interleukin-18