PROTECTIVE ROLE OF MTARC1 RS2642438 POLYMORPHISM AGAINST FIBROSIS PROGRESSION IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD)

Introduction and Objectives

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide, with fibrosis progression being a key determinant of clinical outcomes. Genetic polymorphisms, such as MTARC1 (rs2642438), have been implicated in modifying fibrosis risk. This study aimed to evaluate the protective role of the MTARC1 AA genotype in protecting against significant fibrosisin Brazilian patients with MASLD.

Patients and Methods

A total of 212 biopsy-proven MASLD patients were included, classified into, Group 1 (F0-F1, n=110): No significant fibrosis. Group 2 (F2-F4, n=102): Significant fibrosis. Additionally, 90 healthy individuals served as controls. Genotyping for MTARC1 (rs2642438) was performed using real-time PCR. Logistic regression models were used to assess the association between MTARC1 genotypes and significant fibrosis, adjusting for metabolic and clinical factors.

Results

The protective AA genotype was significantly more frequent in the control group (52%) than in MASLD patients (5%, p = 2.76×10⁻²⁰).

Patients carrying the AA genotype had an 81% lower risk of developing significant fibrosis (OR = 0.19; 95% CI: 0.08 - 0.45; p < 0.001).

No significant associations were observed for the GG and GA genotypes regarding fibrosis progression.

Conclusions

The MTARC1 rs2642438 AA genotype confers strong protection against fibrosis in MASLD patients, suggesting a potential role in risk stratification and personalized management. Future studies with larger cohorts are needed to confirm these findings and elucidate the molecular pathways involved.

Conflict of interest: None

Frequency