Association Between Interleukin-1A, Interleukin-1B, and Bridging integrator 1 Polymorphisms and Alzheimer’s Disease: a standard and Cumulative Meta-analysis

Abstract

Alzheimer's disease (AD) has been one of the most prevalent health problems among senior population. Interleukin-1A (IL-1A) and IL-1B are two isoforms of IL-1. Recent studies suggested that certain polymorphisms on these two genes are associated with AD. Bridging integrator 1 (BIN1) is considered as common genetic risk factors for AD, whereas different studies have provided various conclusions regarding its role in AD. This study was designed to justify the association between multiple gene polymorphisms and AD through an evidence synthesis approach. We conducted a literature search to identify relevant articles published from 2000 to 2015 from PubMed, Embase, and Cochrane Library, in accordance with inclusion criteria. Pooled odds ratios (ORs) were calculated for the allele model. The effect estimates were summarized by both standard and cumulative meta-analysis. Finally, 54 articles with 88 independent studies were enrolled in this meta-analysis. Mutants in rs1800587 of IL-1A, rs1143634 of IL-1B, rs12989701, and rs744373 of BIN1 were significantly associated with AD onset. The difference effect of same single nucleotide polymorphisms (SNPs) on various ethnicities was also observed in our results. The present meta-analysis suggested that IL-1A, IL-1B, and BIN1 were candidate genes for AD pathogenesis. Polymorphisms of IL-1A, IL-1B, and BIN1 are associated with AD onset.

The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ

“…In the subgroup meta-analysis of cytokine polymorphisms, many grouping factors could decrease heterogeneity and improve significance, such as races [ 10 – 14 ], apolipoprotein E (ApoE) ε4 allele and time of AD onset. As for races, it is rare to find significance in Asian and Caucasian populations, and in more extreme cases, a polymorphism indicates higher risk of AD in a population while shows lower risk in the other [ 12 , 13 ].…”

“… MCI AD Plasma/serum CSF Plasma/serum CSF IL-1 family [ 144 ] IL-1α = \ = or ↓ \ -889 C/T (rs1800587) T: ↑ * ↑ in EOAD Meta-analysis [ 145 ] No * in LOAD. * ↑ in Caucasians Meta-analysis [ 14 ] No * in Asians. IL-1β ↑ = ↑or = = or ↑ -511 C/T (rs16944) ?…”

“… *↓ in elderly group of Brazilians Case–control [ 23 ] −511C/−31C/IL1RN1 ? * ↑ in Brazilians Case–control +3953 C/T (rs1143634) T: ↑ * ↑ in non-Asians Meta-analysis [ 15 ], [ 14 ] Exon 5 E1/E2 \ No* in Taiwan population Case–control [ 146 ] IL-1ra \ \ - ↓ [ 139 ] Intron 2 I/II/IV \ IL-18 [ 71 ] = \ = or ↑ ↑ -607 A/C (rs1946518) C: ↑ * ↑ in LOAD of Han Chinese. Case–control [ 20 ] *↑↑ in ApoE ε4 carrier.…”

Alzheimer’s disease risk geneBIN1induces Tau-dependent network hyperexcitability

“…BIN1 was first linked to AD in early genome-wide associated studies (GWAS) (Harold et al, 2009;Seshadri et al, 2010) and remains second only to APOE in genomewide significance in the recent meta-analysis of 94,437 individuals by the International Genomics of Alzheimer's Disease Project (Kunkle et al, 2019). This association has been replicated in datasets with subjects from diverse genetic backgrounds (Carrasquillo et al, 2011;Hollingworth et al, 2011;Hu et al, 2011;Lambert et al, 2011;Lee et al, 2011;Logue et al, 2011;Naj et al, 2011;Wijsman et al, 2011;Kamboh et al, 2012;Chapuis et al, 2013;Lambert et al, 2013;Liu et al, 2013;Miyashita et al, 2013;Reitz et al, 2013;Li et al, 2015;Dong et al, 2016;Rezazadeh et al, 2016;Wang et al, 2016). Further, unbiased epigenetic analyses have provided independent evidence linking BIN1 to AD pathogenesis in several epigenome-wide association studies examining DNA methylation patterns in brain tissue from AD patients, in which BIN1 again emerged as a top hit (De Jager et al, 2014;Chibnik et al, 2015;Yu et al, 2015).…”

Alzheimer’s disease risk gene BIN1 induces Tau-dependent network hyperexcitability

“…BIN1 was first linked to AD in early genome-wide associated studies (GWAS) ( Harold et al, 2009 ; Seshadri et al, 2010 ) and remains second only to APOE in genome-wide significance in the recent meta-analysis of 94,437 individuals by the International Genomics of Alzheimer’s Disease Project ( Kunkle et al, 2019 ). This association has been replicated in datasets with subjects from diverse genetic backgrounds ( Carrasquillo et al, 2011 ; Hollingworth et al, 2011 ; Hu et al, 2011 ; Lambert et al, 2011 ; Lee et al, 2011 ; Logue, 2011 ; Naj et al, 2011 ; Wijsman et al, 2011 ; Kamboh et al, 2012 ; Chapuis et al, 2013 ; Lambert et al, 2013 ; Liu et al, 2013 ; Miyashita et al, 2013 ; Reitz et al, 2013 ; Li et al, 2015 ; Dong et al, 2016 ; Rezazadeh et al, 2016 ; Wang et al, 2016 ). Further, unbiased epigenetic analyses have provided independent evidence linking BIN1 to AD pathogenesis in several epigenome-wide association studies examining DNA methylation patterns in brain tissue from AD patients, in which BIN1 again emerged as a top hit ( De Jager et al, 2014 ; Chibnik et al, 2015 ; Yu et al, 2015 ).…”