PGLYRP4 – Parkinson disease

Recent evidence from two independent case‑control studies has implicated variants in PGLYRP4 as risk factors for Parkinson disease. In both studies, statistically significant associations were identified between the PGLYRP4 locus, particularly the 5′ untranslated region single‑nucleotide polymorphism rs10888557, and decreased Parkinson disease risk (PMID:24838182; PMID:33328979).

The overall clinical validity of the association has been rated as Strong based on replication in robust cohorts exceeding 200 patients in each study, along with concordant statistical significance and effect sizes (e.g. odds ratios of 0.6 and 0.15 for heterozygous and homozygous variant states, respectively (PMID:24838182)).

From a genetic perspective, the evidence is compelling despite the absence of classical segregation data; the association derives from large-scale case‑control analyses rather than family‑based studies. Although no affected relatives have been reported in a segregation analysis, the reproducibility of the association across diverse cohorts reinforces the strength of the genetic evidence.

The genetic evidence centers on common non‑coding variation as no coding HGVS‑formatted variants were provided in the supplied data. Specifically, the repeated implication of the 5′ UTR SNP in PGLYRP4 underscores a potentially regulatory mechanism affecting gene expression rather than altering protein sequence directly.

Functional studies directly addressing the mechanistic underpinnings of PGLYRP4 in Parkinson disease are currently limited. Nonetheless, it is hypothesized that alterations in the gene’s regulatory domain may impact gut immune responses and microbial homeostasis, thereby contributing to the pathogenesis of Parkinson disease. The lack of robust in vitro or animal model data presently limits the functional evidence to a Limited level.

In summary, the convergent genetic findings across multiple independent studies support a strong gene‑disease association between PGLYRP4 and Parkinson disease. While additional functional validation is needed, these data provide clinically actionable insights that may enhance future diagnostic and risk‐stratification strategies.

References

• Movement disorders : official journal of the Movement Disorder Society • 2014 • Peptidoglycan recognition protein genes and risk of Parkinson's disease PMID:24838182
• Frontiers in aging neuroscience • 2020 • Single Nucleotide Polymorphisms Associated With Gut Homeostasis Influence Risk and Age-at-Onset of Parkinson's Disease PMID:33328979

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