Supplementary Material for: Association Study and Meta-Analysis of Polymorphisms, Methylation Profiles, and Peripheral mRNA Expression of the Serotonin Transporter Gene in Patients with Alzheimer's Disease

Background/Aim: The aim of this study was to elucidate the relationship between Alzheimer's disease (AD) and the serotonin transporter gene (SLC6A4). Methods: AD subjects (n = 43) and controls (n = 47) were recruited and evaluated. In leukocytes, we evaluated two polymorphisms in SLC6A4, the serotonin transporter length polymorphic region (5-HTT-LPR) and rs25531, as well as methylation rates of theSLC6A4 promoter region and the SLC6A4 mRNA expression level. We also performed a meta-analysis to examine the relationship between the frequency of the L allele and the risk of AD. Results: The distributions of 5-HTT-LPR and rs25531 polymorphisms in AD subjects were not different from those of controls. Although the methylation rates in AD subjects were not significantly different from those of controls, the expression level in AD subjects was significantly higher than in controls. Additionally, the expression level in AD subjects was significantly correlated with apathy. Meta-analysis revealed that the L/L genotype significantly reduced the risk of AD, but only in the Caucasian population. Conclusion: Higher SLC6A4 mRNA expression in leukocytes in AD was associated with apathy regardless of SLC6A4 genotypes and methylation rates of the promoter region. The L/L genotype may reduce the risk of AD in the Caucasian population.