Association between rs738409 and rs2896019 single-nucleotide polymorphisms of phospholipase domain-containing protein 3 and susceptibility to nonalcoholic fatty liver disease in Greek children and adolescents.

Background: Several studies have detected a strong association linking rs738409 and rs2896019 polymorphisms in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene with hepatic steatosis and steatohepatitis. In the present study we aimed to determine the association of those PNPLA3 variants with nonalcoholic fatty liver disease (NAFLD) susceptibility in obese and nonobese Greek children and adolescents.

Methods: The study recruited 91 children and adolescents of Greek descent with NAFLD or biopsy-proven nonalcoholic steatohepatitis, and 91 healthy subjects of normal weight (control group) with sex distribution similar to the patient group. DNA samples were amplified using polymerase chain reaction with specifically designed primers. Data were analyzed using the statistical software SPSS version 24.0.

Results: A significant correlation was shown between the rs738409 polymorphism (CG and GG genotypes) and the rs2896019 polymorphism (TG genotype) with the development of hepatic steatosis (P<0.001). The incidences of rs738409 GG, rs738409 CG and rs2896019 TG genotypes were found to be increased in patients with hepatic steatosis (obese and nonobese), but not in obese patients without liver disease. The combined expression of the 2 polymorphisms was associated with a lower age of diagnosis of hepatic steatosis in nonobese patients.

Conclusions: We confirmed a strong association between the 2 polymorphisms and hepatic steatosis. The association of the rs2896019 single-nucleotide polymorphism with hepatic steatosis in obese and nonobese pediatric patients, and the combined study of both polymorphisms in a pediatric population of Greek origin are described for the first time.