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.
As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials.
The development of HCC was independently associated with PNPLA3 rs738409 (OR<sub>adjusted</sub> 1.84 [95% CI 1.55-2.18], p = 1.85 × 10<sup>-12</sup>) and TM6SF2 rs58542926 (OR<sub>adjusted</sub> 1.66 [1.30-2.13], p = 5.13 × 10<sup>-05</sup>), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR<sub>adjusted</sub> 1.04 [0.88-1.24], p = 0.61) was not significant.
The results suggest that the I148M/PNPLA3 (rs738409) polymorphism is associated with the presence of pCAD in T2DM patients and with some cardiometabolic parameters.
Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis.
In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes.
These findings provide evidence that the PNPLA3 SNP rs738409 contributes to risk for increased liver fat content in African Americans with T2DM, an effect that appears to be independent from serum lipids.
A single nucleotide polymorphism (SNP) rs2072907 in the adiponutrin gene (ADPN) was not associated with obesity and type 2 diabetes in Chinese population.