Common variant in PTK2B is associated with late-onset Alzheimer's disease: A replication study and meta-analyses

Emerging evidence indicates that protein tyrosine kinase 2β (PTK2B) is involved in the pathogenesis of Alzheimer's disease (AD). Recently, a large, two-stage meta-analysis of genome-wide association study (GWAS) confirmed that PTK2B was correlated with an increased risk of AD in Caucasian populations. The aim of this study was to investigate the association between PTK2B polymorphism rs28834970 and the risk of LOAD in a Han Chinese population. A total of 984 sporadic LOAD patients and 1,354 healthy age- and sex-matched control subjects from the Han Chinese population were included in this study. Our results showed no significant differences in the frequency of rs28834970 alleles and genotypes between AD cases and controls. However, meta-analysis of 82,513 individuals confirmed that rs2883490 within PTK2B increased the risk of LOAD (OR = 1.09, 95%CI = 1.07-1.12). Additionally, when these data were stratified by APOEε4 status, the difference of allele frequency was evident in APOEε4 carriers (P = 0.027, OR = 1.423, 95%CI = 1.041-1.945), and positive associations were also observed under an additive model in APOEε4 carriers (P = 0.041, OR = 1.384, 95%CI = 1.014-1891). In summary, our study provides that PTK2B polymorphism (rs28834970) could modify the risk of LOAD, and PTK2B polymorphism (rs28834970) and APOE may interact to increase LOAD risk in a Han Chinese population.