Interleukin-1A polymorphism is not associated with late onset Alzheimer's disease
Over the past few years, association studies have proposed a number of potential genetic risk factors for Alzheimer's disease (AD). With the exception of the varepsilon4 allele of the apolipoprotein E gene, whose association with the late onset type of AD (LOAD) has been confirmed, the relative significance of most of these associations is still in question. A polymorphism in the interleukin-1A gene (IL-1A2) has been suggested as a risk factor for the early onset as well as for LOAD. In this study, the distribution of IL-1A alleles was examined in a cohort of predominantly LOAD patients and in control individuals. No significant difference was detected in genotype or allele frequencies (odds ratios of 0.929 and 0.743, respectively; P>0.5). We conclude that IL-1A genotype is not a major risk factor for LOAD.
- "e l s e v i e r . c o m / l o c a t e / m g e n e Grimaldi et al., 2000; Minster et al., 2000; Nicoll et al., 2000; Rebeck, 2000; Ki et al., 2001; Prince et al., 2001; Combarros et al., 2002; Fidani et al., 2002; Green et al., 2002; Hedley et al., 2002; Mattila et al., 2002; Pirskanen et al., 2002; Pola et al., 2002; Shibata et al., 2002; Clarimon et al., 2003; Depboylu et al., 2003; Faltraco et al., 2003; Kuo et al., 2003; Licastro et al., 2003; Lio et al., 2003; Ma et al., 2003; McCarron et al., 2003; Sciacca et al., 2003; Tsai et al., 2003; Arosio et al., 2004; Capurso et al., 2004; Depboylu et al., 2004; Hayes et al., 2004; Li et al., 2004; McCulley et al., 2004; Nishimura et al., 2004; Scassellati et al., 2004; Zhang et al., 2004; Koivisto et al., 2005; Ma et al., 2005; Seripa et al., 2005; Wang et al., 2005; Culpan et al., 2006; Ramos et al., 2006; Ravaglia et al., 2006; Zhou et al., 2006; Bagnoli et al., 2007; Wang et al., 2007; Combarros et al., 2008; Deniz-Naranjo et al., 2008; Paradowski et al., 2008; Dursun et al., 2009; Hu et al., 2009; Klimkowicz-Mrowiec et al., 2009; Serretti et al., 2009; Vural et al., 2009; Capurso et al., 2010; Combarros et al., 2010; Klimkowicz-Mrowiec et al., 2010; Ribizzi et al., 2010; Shawkatova et al., 2010; Cousin et al., 2011; Vendramini et al., 2011; Heun et al., 2012; Mansoori et al., 2012; Payao et al., 2012; Moraes et al., 2013; Rasmussen et al., 2013; Torres et al., 2013; Flex et al., 2014; Kang et al., 2014; Tian et al., 2015; Toral-Rios et al., 2015). However, these epidemiological studies have reported inconsistent results. "
[Show abstract] [Hide abstract] ABSTRACT: The polymorphism (rs1800587) in the 5'-flanking regulatory region at -889 of the interleukin-1alpha gene has been shown to be associated with inflammatory diseases and Alzheimer's disease (AD). The aim of the current study is to determine whether there is an association between the promoter region polymorphism of the interleukin-1alpha gene and late-onset AD in a cohort of Turkish patients. One hundred and four subjects with dementia of the Alzheimer type and 103 age-matched controls were genotyped according to the PCR with confronting two-pair primers method. Although the distribution of genotypes did not significantly differ (p = 0.107), the difference between allelic frequency was nearly significant according to a chi(2) test (p = 0.05) when the controls and patients were compared. Our results showed that there is no association between the -889 C/T transition on the interleukin-1alpha gene and late-onset AD in the Turkish population.0Comments 11Citations
- "Therefore, confirmatory studies are needed. Expressions of several cytokine mRNA were reported to be increased by  . Both microglia and astrocytes inducing overexpression of interleukin-1 have also been shown in the AD brain404142 . "
[Show abstract] [Hide abstract] ABSTRACT: Increased risk of Alzheimer's disease (AD) has been associated with polymorphisms in the IL-1 gene cluster, and in particular with the IL-1alpha-889 T/T genotype. However, this association is still unclear, and needs further investigation. In order to clarify the role of these polymorphisms in the complex pathogenesis of AD we examined genotype and haplotype frequencies of the two C-to-T SNPs at position -889 and -551 in the IL-1alpha and IL-1beta genes, respectively, and of the 86 bp VNTR intron-2 polymorphisms in the IL-1Ra gene. The analysis was performed in two genetically and diagnostically distinct groups of sporadic AD from Italy and the USA. In the Italian group a significant association between the IL-1alpha-889 T/T genotype and AD (OR=3.022, 95% CI: 1.001-9.119) was found, whereas no difference was found in the group from the USA. Results were also compared with previously published studies that analyzed the same IL-1 polymorphisms in AD. In both groups, the analysis of the estimated haplotypes shows that AD patients and controls who carry the IL-1beta-511 C allele, were also more frequently carriers of the IL-1Ra 1 allele (haplotypes -C-1). The total frequency of the two -C-1 haplotypes (C-C-1 plus T-C-1) was about one half of the total frequency of the eight estimated haplotypes. This was confirmed by significant linkage disequilibrium between these two loci in both the Italian and USA groups. In the Italian group a weak association of the T-C-2 haplotype with the disease (OR=1.648, 95% CI: 1.519-1.788) was also found, whereas in the USA group no difference was found. Although ours and other published data on different samples of Caucasian and non-Caucasian AD show a great heterogeneity in the frequencies of the IL-1alpha-889, the IL-1beta-511 and the IL-1Ra VNTR gene polymorphisms, we confirm the role of the IL-1alpha-889 T/T genotype as a risk factor for sporadic AD, and show the presence of an allelic association between IL-1beta C and IL-1Ra 1 alleles in both the Italian and the USA groups, confirmed by the presence of significant levels of linkage disequilibrium between these two loci.0Comments 42Citations
- "Among common population polymorphisms recently associated with AD, such as those for the genes of 2 -macroglobulin , 1 -antichymotrypsin , angiotensin-converting enzyme (ACE) , methylenetetrahydrofolate reductase (MTHFR) [50,58] and others, new evidence suggests that susceptibility to AD may be associated to polymorphisms in genes that affect the inflammatory cascade . Recently, in fact, polymorphisms in the genes coding for the proinflammatory interleukins-1 (IL-1) and (IL-1) have been associated with both late-and early-onset AD [13,20,22,43,49], although other studies did not confirm this association [15,17,30,39,44]. Inflammatory processes most certainly play an important role in the pathogenesis of AD. "