The Association Of LRRK2Variants With Alzheimer’s Disease Of Han Chinese Population

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. Along with the increasing age, the incidence of AD will increase.1/3of people over85years old suffer from AD, which brings much trouble to family and society. The cause of sporadic AD (SAD) is not very clear and is considered to be caused by the combined effect of environment and genes.Parkinson’s disease (PD) may share some overlapping etiologies in pathogenesis. Mutations of leucine-rich repeat kinase2(LRRK2) can not only lead to the occurrence of late-onset familial type of Parkinson’s disease, and significantly associated with sporadic Parkinson’s disease. We conducted a case control study in the Han Chinese population to investigate two Asian specific LRRK2variants, G2385R and R1628P, with the association of sporadic AD (SAD).Objectives:To investigate the association between ApoE genotypes and AD. To investigate the association between LRRK2G2385R variant and AD as well as R1628P variant and AD.Methods:390patients with AD and545cognitively-normal control individuals were genotyped for the ApoE alleles by amplification refractory mutation system (ARMS). We checked the LRRK2G2385R and R1628P genotype with PCR and digested with restriction enzyme. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio (OR) for developing AD and mean age at onset in different genotypes were calculated using Logistic regression analysis and t-test respectively.Results:The frequencies of ε2allele and ε2(+) genotype were much lower in AD groups compared to NC groups. However, those of ε4allele and ε4(+) genotype were significantly higher. There’s no significantly difference of G2385R genotype between AD and NC groups. The frequency of the C allele within the R1628P variant was more than three times higher in control group (1.7%) than in SAD patients (0.5%)(OR0.264;95%CI,0.088-0.792, P=0.018), indicating that the minor allele C may play a protective role in SAD. After stratification by the presence of one or two APOE ε4alleles, the protective effect becomes stronger (ε44:OR0.028;95%CI,0.003-0.303, P=0.003; s4:OR0.104;95%CI,0.013-0.818, P=0.031).Conclusion:ApoEs4is a risk factor for developing AD while ApoEε2is a protective factor. G2385R has no association with AD. The LRRK2R1628P variant plays a protective role in Han Chinese population with SAD and such effect has an interaction with the APOE genotype. Our study suggested that the LRRK2R1628P variant plays a protective role in Han Chinese population with SAD and such effect has an interaction with the APOE genotype.