HIP1R – Parkinson Disease

The association between HIP1R and Parkinson disease is supported by multiple robust genome‑wide studies. In a meta‑analysis involving 3,212 PD cases (PMID:33987465), HIP1R emerged as one of several loci with suggestive association with PD motor subtype, bolstering its role as a potential modifier of clinical presentation. The findings were statistically significant and contributed to the growing body of genetic risk evidence for Parkinson disease.

A large‑scale replication study evaluated 11 SNPs in 8,750 PD cases and 8,955 controls (PMID:22786590), and HIP1R was among the genes showing a significant susceptibility effect. This independent replication across a diverse cohort supports the reliability and generalizability of the genetic association with PD. The observed per‑allele odds ratios and protective effects in other markers collectively corroborate the role of HIP1R in modifying disease risk.

A case–control study in a Chinese Han population (515 PD patients and 518 controls) further substantiated the involvement of HIP1R, where the rs12817488 polymorphism in the CCDC62/HIP1R locus was significantly associated with PD (PMID:25818163). Notably, gender‑specific analysis revealed differences in allele frequencies, suggesting that HIP1R may contribute to PD risk in a population‐ and sex‑dependent manner. These findings highlight the complexity and multifactorial nature of HIP1R’s involvement in Parkinson disease.

Although direct family segregation data were not provided in these studies, the collective genetic evidence from large-scale cohorts is compelling. The replication of association signals in independent, ethnically diverse populations solidifies the clinical validity of HIP1R as a PD risk factor. Current data indicate that while traditional segregation evidence is lacking, the statistical associations across studies enhance confidence in its relevance for diagnosis and risk assessment.

Assessment of experimental evidence specific to Parkinson disease is limited. To date, no functional assays have directly demonstrated the mechanistic role of HIP1R in PD pathogenesis. However, ancillary studies have revealed that HIP1R is involved in neuronal function and endocytosis, processes that are crucial for maintaining synaptic integrity and may have indirect implications in PD. Future functional studies are needed to elucidate the precise biological mechanisms underlying HIP1R’s contribution to Parkinson disease.

Key take‑home sentence: HIP1R shows strong genetic association across multiple well-powered studies, making it a valuable marker for future diagnostic and therapeutic strategies in Parkinson disease.

References

• Neurology. Genetics • 2021 • Genome-Wide Association Study Meta-Analysis for Parkinson Disease Motor Subtypes PMID:33987465
• Neurology • 2012 • Large-scale replication and heterogeneity in Parkinson disease genetic loci PMID:22786590
• Journal of clinical neuroscience • 2015 • The single nucleotide polymorphism Rs12817488 is associated with Parkinson's disease in the Chinese population PMID:25818163

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