Association of LRRTM3 polymorphisms with late-onset Alzheimer's disease in Han Chinese

The leucine-rich repeat transmembrane 3 (LRRTM3) has been defined as a positional and functional candidate gene for Alzheimer's disease. Recently, four novel variants (rs16923760, rs1925608, rs1925609 and rs10997477) within LRRTM3 were reported to be associated with late-onset Alzheimer's disease (LOAD) in Caucasians. To evaluate the association of the LRRTM3 polymorphisms with LOAD in Asians, we performed a case-control study of 2287 unrelated subjects (1129 cases and 1158 age- and gender-matched controls) in Han Chinese. The rs10997477 T allele was significantly associated with a decreased risk of LOAD in APOE ε4 allele noncarriers (OR=0.750, PC<0.001). Besides, the rs16923760 C allele significantly increased the risk of LOAD in APOE ε4 allele carriers (OR=1.837, PC<0.001). The genotype distribution of rs1925609 polymorphism also significantly differed in APOE ε4 allele noncarriers (PC=0.008). Moreover, the association was further demonstrated in multivariate logistic regression analysis (rs10997477: Recessive model: OR=0.156, PC=0.004; Additive model: OR=0.731, PC<0.001; rs16923760: Dominant model: OR=1.944, PC=0.024; Additive model: OR=1.885, PC<0.001; Recessive model: OR=3.565, PC=0.010; rs1925609: Recessive model: OR=0.421, PC=0.024). As for rs1925608, we failed to detect any association with LOAD. This study firstly provides the independent evidence that the LRRTM3 polymorphisms may play a role in the pathogenesis of LOAD in a Northern Han Chinese population. However, additional independent replication groups are required to further validate this association.