Recently, two CpG sites in ankyrin 1 (ANK1) gene were identified to be hypermethylated and associated with Alzheimer's disease (AD)-related neuropathology in two large independent studies. Genetic variations are indicated to be involved in DNA methylation, especially when the associated single-nucleotide polymorphisms (SNPs) are located adjacent to the CpG site. Accordingly, ANK1 polymorphisms might contribute to late-onset AD (LOAD) risk. One polymorphism rs515071 was identified to be a potential risk factor for type 2 diabetes (T2D). As shared genetic background was found underlying T2D and AD, we postulate that rs515071 polymorphism may be associated with late-onset AD (LOAD) risk and assessed the association in 982 LOAD patients and 1346 sex- and age-matched healthy controls. Our results showed that minor allele A of rs515071 significantly increased LOAD risk in the APOE ε4 (+) subgroup (genotype P = 0.015, allele P = 0.020). After adjusting for age and gender, the association remained significant under the dominant model (OR = 1.809, 95 % confidence interval (CI) = 1.186-2.757, P = 0.006). In conclusion, our findings demonstrate that rs515071 in ANK1 is a novel genetic risk for LOAD susceptibility in Han Chinese.
Keywords: ANK1; Alzheimer’s disease; Association study; Polymorphism.