Relationship between PNPLA3 rs738409 polymorphism and decreased kidney function in children with NAFLD

Abstract

Emerging evidence suggests that patatin‐like phospholipase domain‐containing protein‐3 (PNPLA3) rs738409 genotype (the major genetic variant associated with susceptibility to non‐alcoholic fatty liver disease [NAFLD]) is associated with decreased kidney function in adults. Currently, it is uncertain whether this association also occurs in children/adolescents and whether any association is independent of liver disease severity. We enrolled a sample of 142 consecutive Caucasian children and adolescents with biopsy‐proven NAFLD, presenting to the Liver Unit of the “Bambino Gesù” Children's Hospital. Glomerular filtration rate (e‐GFR) was estimated using the Bedside Schwartz equation, whereas 24‐hour proteinuria was measured with a radioimmunoassay method. Genotyping for PNPLA3 rs738409 genotype was undertaken using the TaqMan SNP genotyping allelic discrimination method. Overall, forty‐five children had G/G, 56 had G/C and 41 had C/C PNPLA3 rs738409 genotype, respectively. Children with G/G genotype had significantly lower e‐GFR (107.5±20 vs. 112.8±18 vs. 125.3±23 mL/min/1.73 m2, p=0.002) and higher 24‐hour proteinuria (58.5±21 vs. 53.9±22 vs. 42.9±20 mg/day, p=0.012) compared to those with either G/C or C/C genotypes. After adjustment for age, sex, systolic blood pressure, measures of adiposity, HOMA‐estimated insulin resistance and biopsy‐confirmed non‐alcoholic steatohepatitis (NASH) and stage of liver fibrosis, the presence of rs738409 G/G genotype was independently associated with both lower e‐GFR (β coefficient: ‐23.6, 95% CI ‐36.3 to ‐10.8, p<0.001) and higher 24‐hour proteinuria (β coefficient: 15.3, 95% CI 1.12 to 30.5, p=0.046).

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ORCID for Christopher Byrne: orcid.org/0000-0001-6322-7753

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