Research ReportGenetic association of TLR4/11367 polymorphism with late-onset Alzheimer's disease in a Han Chinese population

The amyloid beta-protein (A-β) deposits in the brains of patients with Alzheimer's disease (AD) are closely associated with innate immune responses that were assumed to play a pivotal role in the pathogenesis of AD. Toll-like receptor 4 (TLR4) is thought to contribute to Aβ clearance. Studies have reported the presence and functional significance of the TLR4/11367 polymorphism in a Han Chinese population. To evaluate the involvement of the TLR4/11367 polymorphism in the risk of late-onset Alzheimer's disease (LOAD), we performed a case-control study to analyze the genotype and allele distributions of the TLR4/11367 polymorphism in a Han Chinese population (137 LOAD cases and 137 healthy controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P < 0.001, allele P < 0.001). After stratification by APOE ε4-carrying status, the C allele of the TLR4/11367 polymorphism was still significantly associated with LOAD in APOE ε4 non-carriers (OR = 5.77, 95% CI = 3.03-11.00, P < 0.001) and carriers (OR = 2.03, 95% CI = 1.03-3.98, P = 0.04). In addition, a logistic regression analysis also conferred positive association between TLR4/11367C and LOAD (dominant model: ORa = 3.08, 95% CI = 1.60-5.93, P = 0.001; recessive model: ORa = 8.79, 95% CI = 3.31-23.36, P < 0.001; additive model: ORa = 2.75, 95% CI = 1.73-4.37, P < 0.001) after adjustment for age, gender, and the APOE ε4 carrier status. This study gives the first evidence that the TLR4/11367 polymorphism was associated with LOAD in a Han Chinese population.

Research Highlights►Genotype CC was more common in patients with AD. ►The minor allele of TLR4/11367 is a risk factor for LOAD. ►TLR4/11367 polymorphism is associated with LOAD in Han Chinese.