Genetic Analysis of Metabolic-associated Steatosis Liver Disease in a Colombian Cohort

Numerous studies have identified genetic variations linked to the development and progression of Metabolic Associated Steatosis Liver Disease (MASLD), but their relevance is not completely understood in Latin American populations.

To assess the prevalence and frequency of gene variants in their association to MASLD in a Colombian cohort.

We evaluated DNA samples from the Colombian ESCALON cohort (142 MASLD, 46 controls) for the association between the PNPLA3, TM6SF2, MBOAT7, HSD17B13, STAT4, TLL1 and GCKR1 single nucleotide polymorphisms (SNP) (genotyped using TaqMan-genotyping assays) and the presence of advanced fibrosis and cirrhosis (measured by elastography). Initial analyses were conducted for each gene individually, followed by assessments of gene combinations to explore interactions among variants.

The PNPLA3 gene exhibited the G risk allele in 84.4% of patients with MASLD and was the only variant showing significant correlation with advanced fibrosis (p=0.0008), and cirrhosis (p=0.008). In a logistic regression model for advanced fibrosis, four out of six gene combinations showed statistical association with odds ratios (ORs) ranging from 6.8 (99.5% CI 1.4-32.4) to 11.5 (99.5% CI 1.3-103.7). In a logistic regression model for cirrhosis, two out of six gene combinations showed statistical association with ORs ranging from 4.9 (99.5% CI 1.03-22.9) to 7.7 (99.5% CI 1.2-50.2). Adjusted ORs were significant in four gene combinations for advanced fibrosis and in three combinations for cirrhosis.

We found a high prevalence of the PNPLA3 risk allele in association with advanced liver fibrosis and cirrhosis in a Colombian cohort with MASLD.