PILRA – Alzheimer Disease

Recent genetic studies have implicated PILRA in the risk of Alzheimer disease. An exome‑wide burden analysis performed on 132 Alzheimer disease cases reported a significant enrichment of variants in PILRA (PMID:29181857), while a large‐scale meta‑analysis further prioritized PILRA among several risk loci for Alzheimer disease (PMID:33589840). In addition, a candidate SNP study in African American cohorts identified the PILRA rs1859788 A/G allele as conferring a threefold increase in risk (PMID:38408113). Despite these findings, no detailed segregation data or extended family analyses have been reported to date.

Given that Alzheimer disease has a complex genetic architecture, the mode of inheritance in the context of PILRA is best described as complex. The available studies have not demonstrated co‑segregation of variants with disease in families, and thus no additional affected relatives with segregating variants have been documented.

The genetic evidence is comprised primarily of association signals derived from multiple study designs. Although several SNPs have been implicated, no canonical coding variant in strict HGVS nomenclature (i.e. a variant starting with “c.” and including a “(p…)” annotation) was provided in the available literature. Therefore, the reported variant list for PILRA remains empty based on the supplied evidence.

On the functional side, a study investigating the porcine homolog of PILRA identified three splice variants and documented tissue‐specific expression patterns, with significant upregulation of one variant in response to Poly(I:C) stimulation (PMID:26399532). While these findings support a role for PILRA in immune regulation, the direct link between these functional changes and Alzheimer disease pathology remains to be established.

In summary, multiple lines of genetic evidence including exome‑wide burden testing, meta‑analyses, and candidate SNP studies provide moderate support for an association between PILRA and Alzheimer disease. However, limited functional studies and a lack of segregation data underline the need for further comprehensive investigations. Key take‑home sentence: The integration of genetic association data with preliminary functional insights nominates PILRA as a moderate risk factor for Alzheimer disease, with significant implications for diagnostic decision‑making and future therapeutic strategies.

References

• Neuropathology and applied neurobiology • 2018 • Whole‑exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer's disease PMID:29181857
• Nature genetics • 2021 • Genome‑wide meta‑analysis, fine‑mapping and integrative prioritization implicate new Alzheimer's disease risk genes PMID:33589840
• Medwave • 2024 • New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes PMID:38408113
• Yi chuan = Hereditas • 2015 • Cloning and identification of splice variants of the porcine PILRA gene PMID:26399532

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