Association of the p.I148m polymorphism in the PNPLA3 gene with the severity of nonalcoholic fatty liver disease in various clinical groups

Introduction . Non-alcoholic fatty liver disease in most cases is closely associated with diseases such as obesity and type 2 diabetes mellitus, however, this dependence is not observed in a number of patients. In this case, hereditary factors, such as the p.I148M polymorphism of the PNPLA3 gene, play the greatest role in the prognosis of the course of the disease. The objective of the study was to evaluate the effect of the p.I148M polymorphism of the PNPLA3 gene on the course of NAFLD in subgroups of patients with and without concomitant metabolic pathology. Methods and materials. The study group included 212 patients with NAFLD who underwent p.I148M genotyping of the PNPLA3 gene. The severity of the disease was assessed in the general group (group P) and in subgroups of patients with the absence and presence of obesity (subgroups O– and O+, respectively) and type 2 diabetes mellitus (subgroups D– and D+). The severity of the disease was assessed by the severity of cytolytic syndrome (ALT level), hepatic steatosis and fibrosis (the value of CAP and liver stiffness according to transient elastometry) within clinical subgroups between carriers of different PNPLA3 genotypes. Results. Higher ALT levels were found in homozygous carriers of p.I148M compared with the reference genotype (CC/GG) in the subgroups P, D–, D+ and O– (p=0.012; p=0.012; p=0.028 and 0.042, respectively), as well as when comparing the general group of carriers with reference genotype (CC/CG+GG) in subgroups P and D– (p=0.036 and p=0.015). More severe steatosis was found in homozygous carriers compared to the reference genotype (CC/GG) in group P (p=0.017) and subgroup O– (p=0.019). Higher values of liver stiffness were noted in the modified PNPLA3 genotype when comparing the reference (CC/CG) genotype with heterozygotes in group P (p=0.027) and subgroup D– (p=0.006) and when comparing the reference genotype with the general carrier group (CC/CG+GG) in subgroup D– (p=0.009). Conclusions. The carriage of p.I148M of the PNPLA3 gene in patients without metabolic disorders (obesity, type 2 diabetes mellitus) is associated with the formation of cytolytic syndrome, steatosis and liver fibrosis.