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Relationship Between PNPLA3 rs738409 Polymorphism and Decreased Kidney Function in Children With NAFLD
Author(s) -
Targher Giovanni,
Mantovani Alessandro,
Alisi Anna,
Mosca Antonella,
Panera Nadia,
Byrne Christopher D.,
Nobili Valerio
Publication year - 2019
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30625
Subject(s) - nonalcoholic fatty liver disease , medicine , genotype , renal function , liver biopsy , endocrinology , proteinuria , gastroenterology , single nucleotide polymorphism , kidney disease , metabolic syndrome , fatty liver , kidney , biology , biopsy , obesity , disease , genetics , gene
Emerging evidence suggests that patatin‐like phospholipase domain–containing protein‐3 ( PNPLA3 ) rs738409 genotype (the major genetic variant associated with susceptibility to nonalcoholic 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 Caucasian children and adolescents with biopsy‐proven NAFLD, presenting to the Liver Unit of the “Bambino Gesù” Children's Hospital. The glomerular filtration rate (e‐GFR) was estimated using the Bedside Schwartz equation, whereas 24‐hour proteinuria was measured using a radioimmunoassay method. Genotyping for the PNPLA3 rs738409 genotype was undertaken using the single‐nucleotide polymorphism genotyping allelic discrimination method. Overall, 45 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 versus 112.8 ± 18 versus 125.3 ± 23 mL/min/1.73 m 2 , P = 0.002) and higher 24‐hour proteinuria (58.5 ± 21 versus 53.9 ± 22 versus 42.9 ± 20 mg/day, P = 0.012) compared with those with either G/C or C/C genotypes. After adjustment for age, sex, systolic blood pressure, measures of adiposity, homeostasis model assessment–estimated insulin resistance and biopsy‐confirmed nonalcoholic steatohepatitis 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% confidence interval [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). Conclusion : Regardless of established renal risk factors and the histological severity of NAFLD, the PNPLA3 G/G genotype was strongly associated with decreasing kidney function and increasing 24‐hour proteinuria in children/adolescents with histologically confirmed NAFLD.