Nonalcoholic fatty liver disease and eGFR levels could be linked by the PNPLA3 I148M polymorphism in children with obesity

Abstract

Summary Background PNPLA3 I148M polymorphism has an effect on modulation of estimated glomerular filtration rate (eGFR) in nonobese nondiabetic adults and in children with histologically confirmed nonalcoholic fatty liver disease (NAFLD). Objectives The objective of the study is to explore the impact of PNPLA3 I148M polymorphism on eGFR in children with obesity with and without NAFLD. Methods We genotyped 591 patients with obesity for PNPLA3 I148M polymorphism. Anthropometrical, biochemical, and instrumental data were collected. NAFLD was defined by the presence of ultrasound‐detected liver steatosis and/or ALT levels greater than 40 IU/L. Results Patients with NAFLD showed significantly lower eGFR levels compared with subjects without NAFLD. Children with PNPLA3 MM genotype showed lower eGFR levels compared with those with either PNPLA3 IM or II genotypes both in the presence and absence of NAFLD. A general linear model for eGFR variance, including gender, duration of obesity, PNPLA3 genotypes, HOMA, BMI‐SDS, LDL‐C, and triglycerides as covariates, confirmed an inverse association between eGFR and PNPLA3 genotype only in the presence of NAFLD. Conclusions Children with obesity and PNPLA3 MM genotype show lower eGFR levels compared with other genotypes, with a major effect of this polymorphism in the presence of NAFLD.

PNPLA3 gene and kidney disease

“…These findings were also replicated in some cohorts of children and adolescents [28,29], although not in all [30]. For instance, in a sample of nearly 140 overweight children with NAFLD on histology, Targher et al [28], reported that rs738409 G/G genotype was independently associated with both decreasing e-GFR and increasing 24 h urinary protein excretion.…”

“…For instance, in a sample of nearly 140 overweight children with NAFLD on histology, Targher et al [28], reported that rs738409 G/G genotype was independently associated with both decreasing e-GFR and increasing 24 h urinary protein excretion. Another cross-sectional study involving 591 Caucasian children with obesity, it was documented that those with G/G genotype had significantly lower eGFR levels than those with G/C or C/C genotypes [29]. Conversely, in a recent cross-sectional study of 230 Caucasian overweight/obese children, Di Costanzo et al [30], found that children with G/G genotype did not have lower eGFR levels than those with C/G or C/C genotypes.…”

“…Increasing evidence now supports the existence of an association between PNPLA3 G/G genotype and decreasing eGFR values or higher prevalence of CKD across different patient population, even after controlling for many CKD risk factors and for the presence of NAFLD [24][25][26][27][28][29][30] (Table 1). For instance, in a cross-sectional study of 740 Japanese individuals (about 16% of whom had NAFLD on ultrasonography), Oniki et al [24], showed that patients with rs738409 G/G genotype had lower eGFR values than those with G/C or C/C genotypes, even after adjustment for multiple cardio-renal and metabolic risk factors.…”

“…Specifically, some variants related to NAFLD risk, including rs738409, show divergent effects between the traditional metabolic alterations and the development of diseases, especially for cardiovascular complications [6,42]. However, at present, accumulating observational data for rs738409 seems to indicate that this single nucleotide polymorphism might be associated to the presence of CKD [24][25][26][27][28][29][30].…”

“…In the last 5-10 years, several observational reports have documented that imaging-diagnosed NAFLD is independently associated with an increased risk of developing CKD in patients with and without T2DM [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. In addition, accumulating evidence now suggests that the rs738409 G allele is associated with lower values of estimated glomerular filtration rate (eGFR) as well as with a higher risk of CKD in adults but also in adolescents and children, even after adjustment for the presence of NAFLD and multiple CKD risk factors [13,[24][25][26][27][28][29][30]. This association may explain, at least in part, the epidemiological association between liver and kidney disease [10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”