Progranulin (PGRN) plays an important role in Alzheimer's disease (AD) through participating in altering neurite outgrowth and neuronal survival. Previous studies identified that rs5848 in the 3'-untranslated region (3'-UTR) of the PGRN gene (GRN) is strongly associated with AD in Caucasians. In order to assess the involvement of the GRN polymorphism in the risk of late-onset AD (LOAD), we analyzed the genotype and allele distributions of rs5848 in 2350 Han Chinese subjects (AD, 992; control, 1358). The minor T allele of rs5848 was significantly associated with an increased risk of LOAD (P = 0.005, odds ratio (OR) = 1.197, 95 % confidence interval (CI) = 1.057-1.355). Moreover, the association was further validated in the multivariate logistic regression analysis (dominant model: OR = 1.195, P = 0.038, recessive model: OR = 1.386, P = 0.025; additive model: OR = 1.187, P = 0.009). Interestingly, we observed that the interaction between apolipoprotein E (APOE) and rs5848 significantly altered the risk for AD. The rs5848 polymorphism was only significantly associated with LOAD in APOE ε4 allele carriers. Then we included five studies (including the present study) and conducted a meta-analysis which consisted of 3236 cases (male, 1152; female, 2084) and 3405 (male, 1436; female, 1969) controls. The result of the meta-analysis supported T allele of rs5848 within GRN as a risk factor for AD. In conclusion, our results demonstrated that rs5848 polymorphism within GRN was associated with LOAD.

Inositol polyphosphate-5-phosphatase (INPP5D) was reported to be associated with Alzheimer's disease (AD) through modulating the inflammatory process and immune response. A recent genome-wide association study discovered a new locus single nucleotide polymorphism (SNP, rs35349669) of INPP5D which was significantly associated with susceptibility to late-onset Alzheimer's disease (LOAD) in Caucasians. In this study, we investigated the relations between the INPP5D polymorphism rs35349669 and LOAD in Han Chinese population comprising 984 LOAD cases and 1352 healthy controls being matched for age and gender. Our results showed no obvious differences in the genotypic or allelic distributions of rs35349669 polymorphism between LOAD cases and healthy controls (genotype: p = 0.167; allele: p = 0.094). Additionally, when these data were stratified by APOEε4 status, there are still no evident differences in the genotypic or allelic distributions in APOEε4 carriers (p > 0.05). Furthermore, meta-analysis of 81964 individuals confirmed that rs35349669 was significantly associated with the risk for LOAD (OR=1.08, 95%CI=1.06-1.11), but the results remained negative in Chinese subgroup (OR=0.77, 95%CI=0.53-1.13). Overall, the current evidence did not indicate that INPP5D rs35349669 polymorphism play a role in the genetic predisposition to LOAD in Chinese population.

The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) acts as a potential genetic modifier for Alzheimer's disease (AD). Previous reports identified that HMGCR rs3846662 polymorphism is associated with biosynthesis of cholesterol in AD pathology. In order to assess the involvement of the HMGCR polymorphism in the risk of late-onset AD (LOAD) in northern Han Chinese, we performed a case–control study of 2334 unrelated subjects (984 cases and 1350 age- and gender-matched controls) to evaluate the genotype and allele distributions of the HMGCR rs3846662 with LOAD. The genotype distribution (GG, AG, AA) of rs3846662 was significantly different between LOAD patients and controls (P = 0.003), but the allele distribution did not reach a significant difference (P = 0.614). After adjusting for age, gender and the APOE ε4 status, the minor A allele of rs3846662 was validated as a protective factor for LOAD in dominant model (OR = 0.796, P = 0.02, 95% CI = 0.657–0.965). Interestingly, we observed rs3846662 polymorphism was only significantly associated with LOAD in APOE ε4 non-carriers (OR = 0.735, P = 0.005, 95% CI = [0.593, 0.912]). In conclusion, our study demonstrates A allele of HMGCR rs3846662 acts as a protective factor for LOAD in northern Han Chinese.

The myocyte enhancer factor (MEF2) family of transcription factors plays a vital role in memory and learning due to its functions in regulating synapse number and reducing dendritic spines. Myocyte enhancer factor 2 C (MEF2C) is regarded as modulator of amyloid-protein precursor (APP) proteolytic processing, in which amyloid-β (Aβ) is produced. A common single nucleotide polymorphism (SNP, rs190982) in MEF2C gene was identified to be related to late-onset Alzheimer's disease (LOAD) in Caucasians in a large meta-analysis of genome-wide association studies (GWAS). Here, we recruited unrelated 984 LOAD patients and 1348 healthy controls matched for gender and age to ascertain whether the rs190982 polymorphism is related to LOAD in Han Chinese. No difference in the genotype and allele distributions of the MEF2C rs190982 polymorphism was found between LOAD cases and healthy controls (genotype: P = 0.861; allele: P = 0.862), even after stratification for APOE ε4 allele as well as statistical adjustment for age, gender and APOE ε4 status. Furthermore, the meta-analysis in 4089 Chinese individuals did not detect the association of rs190982 within MEF2C with the risk for LOAD (OR = 1.03, 95%CI = 0.90-1.18). Overall, the current evidence did not support the relation between rs190982 polymorphism within MEF2C and the LOAD risk in Northern Han Chinese.

The disrupted-in-schizophrenia-1 (DISC1) is a candidate gene for psychiatric diseases and plays various roles in brain development. It has been reported as a candidate gene for Alzheimer's disease (AD) in a recent large genome-wide association study in Caucasians. To explore the associations between DISC1 and AD, we performed a case-control study including 2318 subjects in Northern Han Chinese. We found that one single nucleotide polymorphism (rs6675281) was associated with the risk of late-onset Alzheimer's disease (LOAD) in northern Han Chinese population. As for rs821616 and rs3738401, no association was detected with LOAD. In conclusion, DISC1 increased the risk for LOAD in northern Han Chinese population.