PNPLA3 gene polymorphism in Brazilian patients with type 2 diabetes: A prognostic marker beyond liver disease?

Genetic factors may impact nonalcoholic fatty liver disease (NAFLD) severity. We aimed to assess the prevalence of patatin-like phospholipase domain-containing 3 protein (PNPLA3) gene rs738409 C > G polymorphism in Brazilian individuals with type 2 diabetes and to investigate its association with liver disease severity, diabetic chronic degenerative complications, and metabolic control.

PNPLA3 genotyping was performed and classified as CC, CG, and GG. Clinical and laboratory data were obtained, including chronic degenerative diabetes complications. Liver stiffness and steatosis were evaluated by transient hepatic elastography with CAP using FibroScan®. Multiple logistic regression was performed to investigate the association of PNPLA3 G allele with clinical and laboratory variables and with hepatic fibrosis/steatosis. Three hundred three patients were included (118 male, mean age 59 ± 9.5 years). The G allele frequency was 32.5% (CC 47%, CG 41%, and GG 12%). Significant liver fibrosis and severe steatosis were diagnosed in 26% and 43% of patients, respectively. The variables independently associated with the G allele were coronary artery disease (OR: 2.25; 95% CI: 1.03-4.88; p = 0.04), better glycemic control (OR for having an HbA_1c ≥ 8% [64 mmol/mol]: 0.53; 95% CI: 0.31-0.89; p = 0.01), and significant liver fibrosis (OR: 1.82; 95% CI: 1.04-3.17; p = 0.03).

In individuals with diabetes and NAFLD, PNPLA3 gene rs738409 C > G polymorphism is a marker for the risk of significant liver fibrosis and cardiovascular disease and may be associated with better glycemic control.