TRPM2 Gene Polymorphism, NLRP3 Inflammasome Expression in Vitiligo Patients

TRPM2 Gene Polymorphism in Relation to NLRP3 Inflammasome Expression in Vitiligo Patients

This study investigates the relationship between Transient Receptor Potential Melastatin 2 (TRPM2) gene polymorphism and Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome expression in patients with vitiligo. Vitiligo is a common autoimmune depigmenting disorder characterized by melanocyte destruction associated with oxidative stress and immune dysregulation.

TRPM2 is a calcium-permeable cation channel activated by oxidative stress, while NLRP3 inflammasome activation promotes inflammation through interleukin-1β (IL-1β) and interleukin-18 (IL-18) release. This study aims to evaluate TRPM2 genetic variants, NLRP3 expression levels, and their possible correlation with disease severity measured using the Vitiligo Area Scoring Index (VASI).

Study Overview

• Status: Active, not recruiting
• Conditions: Vitiligo

Detailed Description

Vitiligo is a chronic autoimmune depigmenting disorder characterized by selective loss of melanocytes. Oxidative stress plays a central role in triggering melanocyte damage. Transient Receptor Potential Melastatin 2 (TRPM2) is a calcium-permeable cation channel activated by reactive oxygen species (ROS). Activation of TRPM2 leads to increased intracellular calcium (Ca2+) influx and mitochondrial dysfunction, contributing to melanocyte apoptosis.

The Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex activated by cellular stress signals, including Ca2+ influx, ROS, and mitochondrial injury. NLRP3 activation results in caspase-1 activation and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18), which further contribute to melanocyte destruction.

Evidence suggests an interaction between TRPM2 activation and NLRP3 inflammasome signaling, particularly under oxidative stress conditions. However, this relationship has not been studied in vitiligo patients. This study investigates TRPM2 gene polymorphism, evaluates NLRP3 expression levels, and explores their association with disease presence and severity.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

Study Locations

• Egypt
  • Aswan Governorate
    • Aswān, Aswan Governorate, Egypt, 81528
      • Aswan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with clinically diagnosed vitiligo attending the Dermatology Department at Aswan University Hospital, Egypt, and healthy control participants matched for age and sex.

Description

Inclusion Criteria:

- Adult patients (aged 18 years and older) clinically diagnosed with vitiligo, either newly diagnosed or not on treatment for at least 3 months before the study.

Exclusion Criteria:

• Any participant with associated inflammatory disease (such as infections or autoimmune disorders).
• Patients with chronic diseases including cardiac, hepatic, hematologic, or renal disorders, or malignancies.
• Patients who had recent major surgical procedures.
• Patients with segmental vitiligo.
• Vitiligo patients who have received treatment within 3 months prior to the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Vitiligo Patients; Participants clinically diagnosed with vitiligo, recruited from the Dermatology Outpatient Clinic, Aswan University Hospital. Peripheral blood samples will be collected for TRPM2 gene and NLRP3 inflammasome analysis.
Healthy Controls; Age- and sex-matched healthy individuals without autoimmune or inflammatory disorders, recruited as controls. Blood samples will be analyzed similarly for comparison.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TRPM2 gene polymorphism in vitiligo patients	Assessment of TRPM2 gene polymorphism by SNP genotyping in blood samples from vitiligo patients and healthy controls. The frequency and distribution of TRPM2 variants will be compared between groups.	At time of enrollment (single visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NLRP3 inflammasome expression in vitiligo patients	Quantification of NLRP3 inflammasome gene expression by real-time PCR (RT-qPCR) in peripheral blood of vitiligo patients and healthy controls. Expression levels will be compared between groups.	At time of enrollment (single visit)
Correlation between TRPM2 polymorphism and NLRP3 inflammasome expression	Correlation analysis between TRPM2 gene polymorphism and NLRP3 inflammasome expression among vitiligo patients to assess possible functional association.	At time of enrollment (single visit)
Association between TRPM2 gene polymorphism and disease severity	Comparison of TRPM2 gene polymorphism variants with vitiligo severity measured by Vitiligo Area Severity Index (VASI). The Vitiligo Area Scoring Index (VASI) is a validated tool used to quantify vitiligo severity. Scores range from 0 to 100, where higher scores indicate greater disease severity. Assessment is performed at a single study visit.	At time of enrollment (single visit)

Collaborators and Investigators

• Sponsor: Aswan University
• Investigators: Principal Investigator: Mostafa Ahmed Maher, M.B.B.Ch., Faculty of medicine, Aswan university

Publications and helpful links

Helpful Links

• Faculty of Medicine, Aswan University official website.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Estimated): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: TRPM2, NLRP3, oxidative stress, inflammasome, genetic polymorphism
• Additional Relevant MeSH Terms: Skin Diseases; Hypopigmentation; Pigmentation Disorders; Skin and Connective Tissue Diseases; Vitiligo
• Other Study ID Numbers: 897/1/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. Summary results will be available in the final thesis and related publications.