PNPLA3 I148M polymorphism influences renal function in children with obesity and prediabetes

Objective: Non-alcoholic fatty liver disease (NAFLD) negatively impacts on renal function with the contribution of the I148M variant in the patatin like phospholipase containing domain 3 (PNPLA3) gene. We hypothesized that children with prediabetes present with lower estimated glomerular filtration rate (eGFR) than those with normal glucose tolerance (NGT) and that the 148M PNPLA3 allele could play a worsening role. We aimed evaluating the influence of the I148M PNPLA3 polymorphism on the relationship between eGFR and prediabetes in children with obesity. Methods: One thousand thirty-six children underwent to complete assessment and were genotyped for the I148M PNPLA3 polymorphism. Results: Patients with prediabetes showed lower eGFR levels (171.03±40.32 vs. 190.80±41.71ml/min/1.73 m2; p=0.001) and higher prevalence of NAFLD (80% vs. 59%; p=0.003) than those with NGT. Children with prediabetes showed lower eGFR levels than those with NGT (150.97±14.56 vs 192.88±40.09; p<0.0001) among carriers of the PNPLA3 148M allele. This was not confirmed among homozygous for PNPLA3 I148 allele. A general linear model for eGFR variance confirmed an inverse and significant association of eGFR with prediabetes in patients carrying the 148M PNPLA3 allele but not in patients homozygous for PNPLA3 I148 allele. Conclusions: Prediabetes negatively affects renal function in children with obesity. This effect is heightened in patients carrying the PNPLA3 148M allele.