O-14 A SYNERGISTIC EFFECT OF PNPLA3 GENE POLYMORPHISM AND INSULIN RESISTANCE INCREASES THE RISK TO NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME

Abstract

The patatin-like phospholipase 3 gene polymorphism (PNPLA3) has been consistently associated with non-alcoholic fatty liver disease (NAFLD) and its histological severity on different populations. In addition, increasing evidence demonstrates the association of NAFLD and polycystic ovary syndrome (PCOS), both associated with obesity, insulin resistance (IR) and metabolic syndrome (MS). Describe the prevalence of the PNPLA3 gene polymorphism and its impact on NAFLD susceptibility and progression in women with PCOS. This was a cross-sectional study enrolling 163 patients with PCOS. All the patients were evaluated for the presence of the PNPLA3 (rs738409 c.444C>G) polymorphism, hepatic steatosis at ultrasound and metabolic disorders. In patients with steatosis, transient hepatic elastography was performed to assess liver stiffness. In this population, evidence of hepatic steatosis was observed in 72.4% of them. The polymorphism was present in heterozygosis (CG) in 41.7% and in homozygosis (GG) in 8% of patients and was not statistically associated with the occurrence of NAFLD or clinically significant fibrosis (≥ F2). IR had a prevalence of 75% and, after evaluation by a multiple regression model, it was the main factor associated with the risk of NAFLD (B = 1.405, p = 0.026). A synergistic effect between IR and the presence of polymorphism on increasing the risk of NAFLD was observed (B = 2.047, p = 0.042). HDL values ≥ 49 mg/dL showed a negative association with NAFLD (B = - 1.578, p = 0.001). MS and IR, waist circumference, higher values of transaminases and lower levels of dehydroepiandrosterone sulfate were associated with clinically significant fibrosis. The PNPLA3 gene polymorphism did not present an independent association either with NAFLD or the development of clinically significant fibrosis in women with PCOS. However, the polymorphism interacts synergistically with IR and increases the risk of NAFLD.