Molecular Characterization of Patatin-Like Phospholipase Domain-Containing 3 (PNPLA3) Gene in Alcoholic Liver Disease

Alcoholic liver disease (ALD) is a significant cause of liver-related morbidity and mortality worldwide. The role of genetic factors, particularly the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, in the progression of ALD remains underexplored in the Indian population. This study aims to investigate the molecular characterization of the PNPLA3 gene polymorphism in individuals with ALD in India.

A cross-sectional study was conducted at Bharatiya Lingayat Development Educational Association (BLDE) (Deemed to Be University), Shri B. M. Patil Medical College Hospital and Research Center, Vijayapura, from May 2023 to December 2024. The study involved 60 patients diagnosed with ALD, confirmed through clinical history, radiological findings, and biochemical parameters. Genetic analysis for PNPLA3 polymorphism was performed using polymerase chain reaction (PCR)-based molecular techniques, and DNA sequencing was carried out to detect the rs738409 and rs738408 mutations. Data analysis was performed using SPSS version 26 (IBM Corp., Armonk, NY), and descriptive statistics and independent sample t-tests were used for comparisons.

Among the 60 study participants, the majority were male 58(96.7%), with a mean age of 41-50 years. The most common disease stage was cirrhosis, 42(70%). Genetic analysis revealed that 49(81.7%) of participants had no detectable mutation, while 5(8.3%) had the rs738409 polymorphism, and 6(10%) had both rs738409 and rs738408 mutations. No significant associations were found between the genetic mutations and demographic or clinical variables. However, laboratory analyses showed significantly higher aspartate aminotransferase (AST) levels and lower leukocyte and platelet counts in mutation-positive individuals compared to those without mutations.

The study identified the presence of PNPLA3 genetic mutations in a small subset of patients with ALD in India. Although the mutations did not show significant associations with demographic or clinical variables, they were associated with altered laboratory parameters, highlighting the potential role of PNPLA3 in the progression of ALD. Further studies are required to validate these findings and understand the genetic basis of ALD in the Indian population.