Effects of PNPLA3 on liver fat and metabolic profile in Hispanic children and adolescents.
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.


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.
Goran
Michael I
MI
Department of Preventive Medicine, Childhood Obesity Research Center, University of Southern California, Los Angeles, California, USA. goran@usc.edu
Walker
Ryan
R
Le
Kim-Anne
KA
Mahurkar
Swapna
S
Vikman
Susanna
S
Davis
Jaimie N
JN
Spruijt-Metz
Donna
D
Weigensberg
Marc J
MJ
Allayee
Hooman
H
D000273:Adipose Tissue / Q000033:anatomy & histology; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics*; D010179:Pancreas / Q000033:anatomy & histology; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D008076:Cholesterol, HDL; D007328:Insulin; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent