Background Mild cognitive impairment (MCI) is an intermediate stage between normal cognition and Alzheimer’s disease (AD). Genome-wide association studies (GWAS) have identified many AD-risk variants and indicated the important role of lipid metabolism pathway in AD progression. This study aimed to investigate the effects of triglyceride (TG) and genetic risk factors on progression from MCI to AD (MCI-AD progression).Methods The current study sample comprised of 305 MCI subjects aged 50 and over who were prospectively followed up for average 4.5 years in a sub-cohort of the Shanghai Aging Study. A consensus diagnosis of incident AD was conducted according to Diagnostic and Statistical Manual of Mental Disorders-IV and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria. Fasting blood samples were obtained at baseline for analyzing serum TG. Single nucleotide polymorphisms (SNPs) genotyping was performed using a MassARRAY system. The effect of TG, genetic variants and their interaction on MCI-AD progression were analyzed using Cox proportional hazards regression model.Results During a mean (±SD) follow-up period of 4.5±1.3 y, 58 subjects developed incident AD. The SNP, rs6859 in the Poliovirus Receptor–Related 2 (PVRL2) gene, was significantly associated with incident AD (false discovery rate (FDR)-adjusted P = 0.018). In multivariate cox model, the PVRL2 rs6859 AG, AA and AG+AA genotypes were associated with significantly increased incident AD, compared with the GG genotype (hazard ratio [HR] = 2.29, P = 0.029, and HR = 2.92, P = 0.013, and HR = 2.47, P =0.012, respectively). In PVRL2 rs6859 AG/AA carriers, higher ln TG was significantly associated with increased risk of incident AD (adjusted HR =2.64, P = 0.034). Ln TG and PVRL2 rs6859 had interactive effect on the MCI-AD progression (P Ln TG × rs6859 = 0.001). Conclusion The present study indicated that PVRL2 rs6859 modified the effect of TG on MCI-AD progression. Precision prevention in MCI population based on genetic information should be considered to avoid progression to AD.
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