Arch. Endocrinol. Metab. 2025;69(6): e240458
Impact of genetic variation in the human leptin gene promoter on metabolic dysfunction-associated steatotic liver disease risk
DOI: 10.20945/2359-4292-2024-0458
ABSTRACT
Objective:
Metabolic dysfunction-associated steatotic liver disease (MASLD), a worldwide public health challenge with a prevalence of around 25%, is strongly related to obesity and insulin resistance. The present study investigated the possible association between MASLD and the leptin gene (LEP) -2548G>A (rs7799039) polymorphism.
Subjects and methods:
A total of 250 subjects (125 biopsy-proven MASLD patients and 125 controls) were genotyped for the -2548G>A promoter variant using the PCR-RFLP technique.
Results:
There was no deviation from Hardy-Weinberg equilibrium for LEP -2548G>A polymorphism in both groups (P > 0.05). A significant association between this gene variant and MASLD was found. The LEP -2548G>A “GG” genotype compared with ‘‘AA+AG’’ genotype was underrepresented in the MASLD patients than controls, even after adjustment for confounding factors (P = 0.016; OR = 0.42, 95% CI = 0.40-0.83).
Conclusion:
For the first time, our findings demonstrated that the “GG” genotype of LEP -2548G>A gene variant can be a potential protective factor for MASLD. Further studies in other populations, however, are required to support this finding.