rs5848 Variant of Progranulin Gene Is a Risk of Alzheimer’s Disease in the Taiwanese Population

Department of Neurology, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan, ROC.
Neurodegenerative Diseases (Impact Factor: 3.51). 05/2011; 8(4):216-20. DOI: 10.1159/000322538
Source: PubMed


Progranulin is the precursor of granulins, and its downregulation may lead to neurodegeneration. The single-nucleotide polymorphism rs5848 increases the risk of Alzheimer's disease (AD). We explored the association between alleles of rs5848 and the risk of AD in the Taiwanese population. The frequency of the homozygous TT genotype (16.4 vs. 10.0%) increased in AD subjects by an odds ratio (OR) of 1.87 (p = 0.03) corrected for APOE ε4, age and gender. Interaction between age and homozygous TT genotype accentuated the risk of AD (OR 4.44, p < 0.001). The homozygous TT genotype of rs5848 may play a role in the genetic risk of AD development, especially in the elderly.

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    • "Although this genetic association could not be replicated in two series of largely clinical FTLD patients [46,47], these results are consistent with PGRN loss as the disease mechanism associated with FTLD-TDP. SNP rs5848 was also reported as a genetic risk factor for the development of hippocampal sclerosis in older people and for the development of Alzheimer's disease in a Taiwanese population [48,49]. Genetic association studies using several other common polymorphisms in the GRN genomic region further identified significant association of GRN variants in Belgian and Finnish Alzheimer's disease populations [40,50], in Belgian and Dutch ALS populations [51], and in an Italian FTLD population [52]. "
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    ABSTRACT: Genetic variants in the granulin (GRN) gene have been shown to increase the risk of Alzheimer's disease (AD). Here, we report that the A allele of rs5848 in GRN reduces plasma granulin levels in a dose-dependent manner in a clinically-defined AD sample cohort. Similarly, the mRNA levels of granulin were decreased with respect to A allele of rs5848 in the inferior temporal cortex of neuropathologically confirmed AD patients. Our findings suggest that the A allele of rs5848 is functionally relevant by reducing the expression of granulin.
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