Background/Aims. Sortilin-related receptor 1 (SORL1) is involved in the neuronal transport processes and plays a role in the formation of amyloid plaques. This study investigated the association of 6 SORL1 single nucleotide polymorphisms (SNPs 8, 9, 10, 13, 19, and 23) with cognitive impairment (CI) in Filipinos. Methods. DNA samples from 484 subjects (100 Alzheimer’s Disease (AD) cases, 109 mild cognitive impairment (MCI) cases, 18 other types of CI, and 257 no dementia controls (NDC)) were genotyped using TaqMan SNP Genotyping Assays. Data Analysis. Our study showed strong linkage disequilibrium in the SNPs 8, 9, and 10 block. Our results showed that CI was significantly associated with SNPs 13 and 23. None of the SORL1 SNPs studied was associated with AD while SNPs 8, 9, 10, and 23 were associated with MCI. Conclusion. The findings had provided evidence that SORL1 may predispose individuals to CI. Further studies are needed to clarify the role of SORL1 in Filipinos with AD. 1. Introduction Sortilin-related receptor 1 (SORL1) is genetically linked to Alzheimer’s disease (AD) [1–7]. Recent evidence indicates that it acts as a regulatory gatekeeper for determining the ultimate destination of amyloid precursor protein (APP) [8]. APP processing generates the β-amyloid (Aβ) peptides, which are deposited as the amyloid plaques in brains of individuals with AD [9]. AD was associated with the “C,” “G,” and “C” alleles at single nucleotide polymorphisms (SNP) 8, 9, and 10, in the 5′-end of SORL1, respectively and the “G” and “T” alleles at SNPs 19 and 23 in the 3′-end of SORL1, respectively [2]. Using frozen brain tissue from autopsy-confirmed AD cases, Lee et al. reported that some AD patients displayed low level of SORL1 [1]. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing AD. Mild cognitive impairment (MCI) refers to individuals who exhibit cognitive deficit but not dementia [10]. It has an incidence rate of 9.9/1000 person-years and an annual conversion rate of 10% to 12% to AD, in contrast to a conversion rate of 1% to 2% in the normal elderly population [11]. Sager et al. reported that MCI subjects with low SORL1 expression levels were significantly more cognitively impaired than subjects with high levels of expressed SORL1 [10]. Currently, there has been no published data on the genetic variation of SORL1 in the Filipino population. In this study, we sought to investigate the role of SORL1 (SNPs 8, 9, 10, 13, 19, and 23) in Filipinos with cognitive impairment (CI), MCI, and AD
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