Systematic Exploration of TRPV6 Variants in Pancreatitis: Unraveling Genetic Associations and Pathophysiological Insights through Comprehensive Systematic Review and In-Silico Analysis

Authors

Omar Alomari, Hamidiye International School of Medicine, University of Health Sciences, Istanbul, TürkiyeFollow
Rumeysa Yegin, Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Türkiye
Muhammed Edib Mokresh, Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Türkiye
Ghazaleh Kokabi Ghahremanpour, Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Türkiye
Nurullah Komurcu, Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Türkiye
Elif Nur Ari, Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey
Magda Wojtara, Department of Human Genetics, University of Michigan Medical School; Ann Arbor, United States
Ali Karaman, Department of Medical Genetics, Istanbul Zeynep Kâmil Women and Children Training and Research Hospital, Istanbul, Türkiye
Abdulqadir J. Nashwan, Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar; Nursing & Midwifery Research Department (NMRD), Hamad Medical Corporation, Doha, Qatar

Abstract

Background and Aims: The transient receptor potential vanilloid subfamily member 6 (TRPV6), a calcium-selective channel, is crucial for intracellular calcium (Ca2+) transport, impacting the maintenance of Ca2+ homeostasis in the pancreas. Variants in the TRPV6 gene have been associated with disruptions in calcium balance, potentially contributing to chronic pancreatitis (CP). This systematic review aims to unravel the connections between TRPV6 gene variants and pancreatitis, with a particular focus on CP. Additionally, we conducted an in-silico co-expression analysis to explore the interrelationships among validated genetic variants associated with pancreatitis pathophysiology and TRPV6 gene variants . Methods: A comprehensive literature search was conducted using PRISMA 2020 guidelines across multiple databases. Eligible studies were screened for original research investigating TRPV6 and pancreatitis relationships. For the in-silico analysis, the STRING database was utilized to explore protein-protein interactions and co-expression relationships between the reported genes in the literature as associated with pancreatitis. Results: Eleven studies met the inclusion criteria, including case-control studies, observational cohort, case reports, and animal studies. Several key TRPV6 variants like p.(Ala18Ser), p.Cys197Arg, p.Met721Tyr, and p.(Val492Tyr)*136 were linked to CP, often in conjunction with variants in other genes like PRSS1 and CFTR, suggesting a complex genetic landscape. Some studies reported that defective TRPV6 variants were associated with disrupted calcium homeostasis, which is crucial in CP development. While the in-silico analysis offered insights into protein-protein interactions involving TRPV6, it did not reveal significant co-expression relationships. Conclusion: TRPV6 variants are implicated in CP pathogenesis, demonstrating phenotypic variability and population-specific associations. Their synergistic effects with other pancreatitis-related variants highlight the complex genetic landscape. This study suggests potential therapeutic approaches and supports the inclusion of TRPV6 into genetic screening panels for CP.

Recommended Citation

Alomari, Omar; Yegin, Rumeysa; Mokresh, Muhammed Edib; Ghahremanpour, Ghazaleh Kokabi; Komurcu, Nurullah; Ari, Elif Nur; Wojtara, Magda; Karaman, Ali; and Nashwan, Abdulqadir J. (2025) "Systematic Exploration of TRPV6 Variants in Pancreatitis: Unraveling Genetic Associations and Pathophysiological Insights through Comprehensive Systematic Review and In-Silico Analysis," Journal of Pediatric Genetics: Vol. 14: Iss. 2, Article 1.
DOI: https://doi.org/10.53391/2146-460X.1011
Available at: https://jpg.researchcommons.org/journal/vol14/iss2/1