YEN-CHING CHENYip P.-K.Huang Y.-L.Sun Y.Wen L.-L.Chu Y.-M.TA-FU CHEN2020-11-032020-11-0320121932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84871296103&doi=10.1371%2fjournal.pone.0050771&partnerID=40&md5=593fc985b3e214046c2f06c81c052bdchttps://scholars.lib.ntu.edu.tw/handle/123456789/519493Background: Toll like receptor 4 (TLR4) has been related to inflammation and beta-amyloid deposition in Alzheimer's disease (AD) brain. No study has explored the association between haplotype-tagging single nucleotide polymorphisms (htSNPs) of TLR4 and AD risk previously and ApoE e4 status alone showed low sensitivity in identifying late-onset AD (LOAD) patients. Methods: A total of 269 LOAD patients were recruited from three hospitals in northern Taiwan (2007-2010). Controls (n = 449) were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency?5%) TLR4 htSNPs were selected to assess the association between TLR4 polymorphisms and the risk of LOAD in the Chinese ethnic population. Results: Homozygosity of TLR4 rs1927907 was significantly associated with an increased risk of LOAD [TT vs. CC: adjusted odds ratio (AOR) = 2.45, 95% confidence interval (CI) = 1.30-4.64]. After stratification, the association increased further in ApoE e4 non-carriers (AOR = 3.07) and in hypertensive patients (AOR = 3.60). Haplotype GACGG was associated with a decreased risk of LOAD (1 vs. 0 copies: AOR = 0.59, 95% CI = 0.36-0.96; 2 vs. 0 copies: AOR = 0.31, 95% CI = 0.14-0.67) in ApoE e4 non-carriers. ApoE e4 status significantly modified this association (pinteraction = 0.01). These associations remained significant after correction for multiple tests. Conclusions: Sequence variants of TLR4 were associated with an increased risk of LOAD, especially in ApoE e4 non-carriers and in hypertensive patients. The combination of TLR4 rs1927907 and ApoE e4 significantly increased the screening sensitivity in identifying LOAD patients from 0.4 to 0.7. ? 2012 Chen et al.[SDGs]SDG3apolipoprotein E4; toll like receptor 4; aged; Alzheimer disease; article; Chinese; controlled study; female; gene; gene frequency; genotype; haplotype; homozygosity; human; hypercholesterolemia; hypertension; major clinical study; male; non insulin dependent diabetes mellitus; population research; risk assessment; risk factor; single nucleotide polymorphism; TLR4 gene; Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease; Apolipoprotein E4; Case-Control Studies; Dementia; Female; Genetic Linkage; Genotype; Haplotypes; Heterozygote; Homozygote; Humans; Hypertension; Inflammation; Male; Models, Genetic; Odds Ratio; Polymorphism, Single Nucleotide; Questionnaires; Risk; Taiwan; Toll-Like Receptor 4journal article10.1371/journal.pone.0050771232720702-s2.0-84871296103