Common variant in GAB2 is associated with late-onset Alzheimer's disease in Han Chinese

Background: GRB-associated binding protein 2 (GAB2) may function as a risk factor in the pathogenesis of Alzheimer disease (AD). A recent large genome-wide association study (GWAS) has identified a significant association of rs10793294 polymorphism within the GAB2 gene with AD in Caucasians. While there are no studies on the association of rs10793294 polymorphism with AD risk in the Chinese population.

Methods: The study investigated 358 sporadic late-onset AD (LOAD) and 366 healthy controls matched for sex and age in a Han Chinese population. The rs10793294 polymorphism within the GAB2 gene was genotyped using MALDI-TOF mass spectrometry.

Results: The C allele of the rs10793294 polymorphism within GAB2 was significantly associated with an increased risk of LOAD (OR=1.33, 95% CI=1.04-1.72, P=0.029). Significance was observed in APOEε4 carriers (genotype P=0.039, allele P=0.016). While in APOE ε4 non-carriers, significant differences were observed in alleles (P=0.039) but not in genotypes (P=0.304). Logistic regression revealed that rs10793294 polymorphism was still strongly associated with LOAD in dominant model (OR=2.58, 95% CI=1.22-5.45, P=0.013) and additive model (OR=1.38, 95% CI=1.05-1.80, P=0.020) after adjusting for age, gender, and the APOE ε4 status.

Conclusions: Our findings implicate GAB2 as a susceptibility gene for LOAD in Han Chinese.