Effects of PNPLA3 on Liver Fat and Metabolic Profile in Hispanic Children and Adolescents

Overview

Journal Diabetes

Specialty Endocrinology

Date 2010 Sep 21

PMID 20852027

Citations 60

Authors

Michael I Goran

Ryan Walker

Kim-Anne Le

Swapna Mahurkar

Susanna Vikman

Jaimie N Davis

Donna Spruijt-Metz

Marc J Weigensberg

Hooman Allayee

Affiliations

Soon will be listed here.

Abstract

Objective: A genome-wide study of adults identified a variant of PNPLA3 (rs738409) associated with ∼twofold higher liver fat. The purpose of this study was to examine the influence of PNPLA3 genotype on liver fat and other related metabolic outcomes in obese Hispanic children and adolescents.

Research Design And Methods: Three hundred and twenty-seven Hispanics aged 8-18 years were genotyped for rs738409. One hundred and eighty-eight subjects had measures of visceral (VAT) and subcutaneous (SAT) adipose tissue volume and hepatic (HFF) and pancreatic (PFF) fat fraction by magnetic resonance imaging. One hundred and thirty-nine subjects did not have HFF measures but had extensive measures of insulin sensitivity and fasting lipids.

Results: Liver fat in GG subjects was 1.7 and 2.4 times higher than GC and CC (11.1 ± 0.8% in GG vs. 6.6 ± 0.7% in GC and 4.7 ± 0.9% in CC; P < 0.0001), and this effect was observed even in the youngest children (8-10 years of age). The variant was not associated with VAT, SAT, PFF, or insulin sensitivity or other glucose/insulin indexes. However, Hispanic children carrying the GG genotype had significantly lower HDL cholesterol (40.9 ± 10.9 in CC vs. 37.0 ± 8.3 in CG vs. 35.7 ± 7.4 in GG; P = 0.03) and a tendency toward lower free fatty acid levels (P = 0.06).

Conclusions: These results provide new evidence that the effect of the PNPLA3 variant is apparent in Hispanic children and adolescents, is unique to fat deposition in liver as compared with other ectopic depots examined, and is associated with lower HDL cholesterol.

Citing Articles

Oxidative gaseous air pollutant exposure interacts with PNPLA3-I148M genotype to influence liver fat fraction and multi-omics profiles in young adults.

Patterson W, Young N, Holzhausen E, Lurmann F, Liang D, Walker D Environ Pollut. 2025; 368:125692.

PMID: 39864653 PMC: 11859754. DOI: 10.1016/j.envpol.2025.125692.

An epidemiological study on the factors including genetic polymorphism influencing ALT >30 U/L and liver fibrosis progression in metabolic dysfunction-associated steatotic liver disease among the general population.

Sato S, Iino C, Sasada T, Soma G, Furusawa K, Yoshida K JGH Open. 2024; 8(12):e70043.

PMID: 39713746 PMC: 11659511. DOI: 10.1002/jgh3.70043.

Ambient air pollution exposure is associated with liver fat and stiffness in Latino youth with a more pronounced effect in those with PNPLA3 genotype and more advanced liver disease.

Schenker R, Machle C, Allayee H, Lurmann F, Patterson W, Kohli R Ecotoxicol Environ Saf. 2024; 286:117234.

PMID: 39454357 PMC: 11578286. DOI: 10.1016/j.ecoenv.2024.117234.

Epidemiological Study on the Interaction between the (rs738409) and Gut Microbiota in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Sato S, Iino C, Sasada T, Soma G, Furusawa K, Yoshida K Genes (Basel). 2024; 15(9).

PMID: 39336763 PMC: 11430940. DOI: 10.3390/genes15091172.

Associations of dietary sugars with liver stiffness in Latino adolescents with obesity differ on PNPLA3 and liver disease severity.

Schenker R, Machle C, Schmidt K, Allayee H, Kohli R, Goran M Liver Int. 2024; 44(8):1768-1774.

PMID: 38634702 PMC: 11251846. DOI: 10.1111/liv.15946.

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