Advertisement

PNPLA3 I148M Polymorphism Influences Renal Function in Children With Obesity and Prediabetes

Published:February 01, 2022DOI:https://doi.org/10.1053/j.jrn.2022.01.007

      Objective

      Nonalcoholic fatty liver disease negatively impacts on renal function with the contribution of the I148 M variant in the patatin-like phospholipase-containing domain 3 (PNPLA3) gene. We hypothesized that children with prediabetes present with a 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 I148 M PNPLA3 polymorphism on the relationship between the eGFR and prediabetes in children with obesity.

      Methods

      One thousand thirty-six children underwent to complete assessment and were genotyped for the I148 M PNPLA3 polymorphism.

      Results

      Patients with prediabetes showed lower eGFR levels (171.03 ± 40.32 vs. 190.80 ± 41.71 mL/min/1.73 m2; P = .001) and higher prevalence of nonalcoholic fatty liver disease (80% vs. 59%; P = .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 < .0001) among carriers of the PNPLA3 148M allele. This was not confirmed among patients homozygous for the PNPLA3 I148 allele.
      A general linear model for eGFR variance confirmed an inverse and significant association of the eGFR with prediabetes in patients carrying the 148M PNPLA3 allele but not in patients homozygous for the PNPLA3 I148 allele.

      Conclusions

      Prediabetes negatively affects renal function in children with obesity. This effect is heightened in patients carrying the PNPLA3 148M allele.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Renal Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Marzuillo P.
        • Grandone A.
        • Di Sessa A.
        • et al.
        Anthropometric and biochemical determinants of estimated glomerular filtration rate in a large cohort of obese children.
        J Ren Nutr. 2018; 28: 359-362
        • Di Bonito P.
        • Valerio G.
        • Licenziati M.R.
        • et al.
        Uric acid, impaired fasting glucose and impaired glucose tolerance in youth with overweight and obesity.
        Nutr Metab Cardiovasc Dis. 2021; 31: 675-680
        • Utzschneider K.M.
        • Tripputi M.T.
        • Kozedub A.
        • et al.
        beta-cells in youth with impaired glucose tolerance or early type 2 diabetes secrete more insulin and are more responsive than in adults.
        Pediatr Diabetes. 2020; 21: 1421-1429
        • Andes L.J.
        • Cheng Y.J.
        • Rolka D.B.
        • Gregg E.W.
        • Imperatore G.
        Prevalence of prediabetes among adolescents and young adults in the United States, 2005-2016.
        JAMA Pediatr. 2019; : e194498
        • Vieira M.B.
        • Neves J.S.
        • Leitao L.
        • et al.
        Impaired fasting glucose and chronic kidney disease, Albuminuria, or worsening kidney function: a secondary analysis of the SPRINT.
        J Clin Endocrinol Metab. 2019; 104: 4024-4032
        • Neves J.S.
        • Correa S.
        • Baeta Baptista R.
        • et al.
        Association of prediabetes with CKD progression and Adverse cardiovascular Outcomes: an analysis of the CRIC study.
        J Clin Endocrinol Metab. 2020; 105: e1772-e1780
        • Li W.
        • Wang A.
        • Jiang J.
        • et al.
        Risk of chronic kidney disease defined by decreased estimated glomerular filtration rate in individuals with different prediabetic phenotypes: results from a prospective cohort study in China.
        BMJ Open Diabetes Res Care. 2020; 8: e000955
        • Echouffo-Tcheugui J.B.
        • Narayan K.M.
        • Weisman D.
        • Golden S.H.
        • Jaar B.G.
        Association between prediabetes and risk of chronic kidney disease: a systematic review and meta-analysis.
        Diabet Med. 2016; 33: 1615-1624
        • Mantovani A.
        • Byrne C.D.
        • Bonora E.
        • Targher G.
        Nonalcoholic fatty liver disease and risk of Incident type 2 diabetes: a meta-analysis.
        Diabetes Care. 2018; 41: 372-382
        • Newton K.P.
        • Hou J.
        • Crimmins N.A.
        • et al.
        Prevalence of prediabetes and type 2 diabetes in children with Nonalcoholic fatty liver disease.
        JAMA Pediatr. 2016; 170: e161971
        • Di Sessa A.
        • Guarino S.
        • Passaro A.P.
        • et al.
        NAFLD and renal function in children: is there a genetic link?.
        Expert Rev Gastroenterol Hepatol. 2021; 15: 975-984
        • Romeo S.
        • Sentinelli F.
        • Cambuli V.M.
        • et al.
        The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life.
        J Hepatol. 2010; 53: 335-338
        • Targher G.
        • Mantovani A.
        • Alisi A.
        • et al.
        Relationship between PNPLA3 rs738409 polymorphism and decreased kidney function in children with NAFLD.
        Hepatology. 2019; 70: 142-153
        • Marzuillo P.
        • Di Sessa A.
        • Guarino S.
        • et al.
        Nonalcoholic fatty liver disease and eGFR levels could be linked by the PNPLA3 I148M polymorphism in children with obesity.
        Pediatr Obes. 2019; 14: e12539
        • Sun D.Q.
        • Zheng K.I.
        • Xu G.
        • et al.
        PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels.
        Liver Int. 2020; 40: 107-119
        • Mantovani A.
        • Taliento A.
        • Zusi C.
        • et al.
        PNPLA3 I148M gene variant and chronic kidney disease in type 2 diabetic patients with NAFLD: clinical and experimental findings.
        Liver Int. 2020; 40: 1130-1141
        • Mantovani A.
        • Zusi C.
        • Sani E.
        • et al.
        Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease.
        Diabetes Metab. 2019; 45: 480-487
        • Karamfilova V.
        • Gateva A.
        • Assyov Y.
        • et al.
        PNPLA3 I148M polymorphism in patients with Nonalcoholic fatty liver disease, obesity and prediabetes.
        J Gastrointestin Liver Dis. 2019; 28: 433-438
        • Cacciari E.
        • Milani S.
        • Balsamo A.
        • et al.
        Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr).
        J Endocrinol Invest. 2006; 29: 581-593
        • Marzuillo P.
        • Guarino S.
        • Furlan D.
        • et al.
        Cleaning the genitalia with plain water improves accuracy of urine dipstick in childhood.
        Eur J Pediatr. 2018; 177: 1573-1579
        • Marzuillo P.
        • Di Sessa A.
        • Umano G.R.
        • et al.
        Novel association between the nonsynonymous A803G polymorphism of the N-acetyltransferase 2 gene and impaired glucose homeostasis in obese children and adolescents.
        Pediatr Diabetes. 2017; 18: 478-484
        • Santoro N.
        • Cirillo G.
        • Lepore M.G.
        • et al.
        Effect of the rs997509 polymorphism on the association between ectonucleotide pyrophosphatase phosphodiesterase 1 and metabolic syndrome and impaired glucose tolerance in childhood obesity.
        J Clin Endocrinol Metab. 2009; 94: 300-305
        • Correia-Costa L.
        • Schaefer F.
        • Afonso A.C.
        • et al.
        Normalization of glomerular filtration rate in obese children.
        Pediatr Nephrol. 2016; 31: 1321-1328
        • American Diabetes A
        Diagnosis and classification of diabetes mellitus.
        Diabetes Care. 2014; 37: S81-S90
        • Di Bonito P.
        • Valerio G.
        • Licenziati M.R.
        • et al.
        High uric acid, reduced glomerular filtration rate and non-alcoholic fatty liver in young people with obesity.
        J Endocrinol Invest. 2020; 43: 461-468
        • Marzuillo P.
        • Di Sessa A.
        • Cirillo G.
        • et al.
        Transmembrane 6 superfamily member 2 167K allele improves renal function in children with obesity.
        Pediatr Res. 2020; 88: 300-304
        • Di Sessa A.
        • Umano G.R.
        • Cirillo G.
        • et al.
        Pediatric non-alcoholic fatty liver disease and kidney function: effect of HSD17B13 variant.
        World J Gastroenterol. 2020; 26: 5474-5483
        • Giudice E.M.
        • Grandone A.
        • Cirillo G.
        • et al.
        The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
        PLoS One. 2011; 6: e27933
        • Tuttle K.R.
        • Alicic R.Z.
        • Duru O.K.
        • et al.
        Clinical Characteristics of and risk factors for chronic kidney disease among adults and children: an analysis of the CURE-CKD Registry.
        JAMA Netw Open. 2019; 2: e1918169
        • Rhee M.
        HbA1c and diabetes: mismatches and Misclassifications.
        J Clin Endocrinol Metab. 2020; 105: e2630-e2632
        • Gonzalez A.
        • Deng Y.
        • Lane A.N.
        • et al.
        Impact of mismatches in HbA1c vs glucose values on the diagnostic classification of diabetes and prediabetes.
        Diabet Med. 2020; 37: 689-696
        • Srivastava T.
        • Alon U.S.
        • Althahabi R.
        • Garg U.
        Impact of standardization of creatinine methodology on the assessment of glomerular filtration rate in children.
        Pediatr Res. 2009; 65: 113-116
        • Marzuillo P.
        • Grandone A.
        • Perrone L.
        • Miraglia Del Giudice E.
        Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease.
        World J Gastroenterol. 2015; 21: 6444-6450