The <i>FAM171A2</i> gene is a key regulator of progranulin expression and modifies the risk of multiple neurodegenerative diseases.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33087363.
- Also identified by DOI 10.1126/sciadv.abb3063 and PMC identifier 7577723.
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Abstract
Progranulin (PGRN) is a secreted pleiotropic glycoprotein associated with the development of common neurodegenerative diseases. Understanding the pathophysiological role of PGRN may help uncover biological underpinnings. We performed a genome-wide association study to determine the genetic regulators of cerebrospinal fluid (CSF) PGRN levels. Common variants in region of <i>FAM171A2</i> were associated with lower CSF PGRN levels (rs708384, <i>P</i> = 3.95 × 10<sup>-12</sup>). This was replicated in another independent cohort. The rs708384 was associated with increased risk of Alzheimer's disease, Parkinson's disease, and frontotemporal dementia and could modify the expression of the <i>FAM171A2</i> gene. FAM171A2 was considerably expressed in the vascular endothelium and microglia, which are rich in PGRN. The in vitro study further confirmed that the rs708384 mutation up-regulated the expression of FAM171A2, which caused a decrease in the PGRN level. Collectively, genetic, molecular, and bioinformatic findings suggested that <i>FAM171A2</i> is a key player in regulating PGRN production.
Medical subject headings
- Frontotemporal Dementia
- Neurodegenerative Diseases
- Progranulins