Source:http://linkedlifedata.com/resource/pubmed/id/20803499
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2010-9-29
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pubmed:abstractText |
The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype (P = 0.005). Although the expression of PNPLA3, PNPLA2, PPAR?2(peroxisome proliferator-activated receptor gamma 2), SREBP1c(sterol regulatory element binding protein 1c), and ACACA(acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and sirtuin 1 (SIRT1) expression (P = 0.04). CONCLUSION: A common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance. The rs738409 PNPLA3 G allele is associated with morphological changes in adipocyte cell size.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/,
http://linkedlifedata.com/resource/pubmed/grant/K24-HD01464,
http://linkedlifedata.com/resource/pubmed/grant/R01 DK49230,
http://linkedlifedata.com/resource/pubmed/grant/R01-EB006494,
http://linkedlifedata.com/resource/pubmed/grant/R01-HD28016,
http://linkedlifedata.com/resource/pubmed/grant/R01-HD40787,
http://linkedlifedata.com/resource/pubmed/grant/UL1 RR0249139
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1527-3350
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pubmed:author |
pubmed-author:BaleAllen EAE,
pubmed-author:CalíAnna MAM,
pubmed-author:CaprioSoniaS,
pubmed-author:CushmanSamuel WSW,
pubmed-author:D'AdamoEbeE,
pubmed-author:DykasDaniel JDJ,
pubmed-author:EldrichSamuelS,
pubmed-author:KursaweRomyR,
pubmed-author:LartaudDerekD,
pubmed-author:NarayanDeepakD,
pubmed-author:PierpontBridgetB,
pubmed-author:SantoroNicolaN,
pubmed-author:SavoyeMaryM,
pubmed-author:ShawMelissa MMM,
pubmed-author:ShulmanGerald IGI,
pubmed-author:ZhangClarence KCK,
pubmed-author:ZhaoHongyuH
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pubmed:issnType |
Electronic
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1281-90
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pubmed:meshHeading |
pubmed-meshheading:20803499-Adipose Tissue,
pubmed-meshheading:20803499-Adolescent,
pubmed-meshheading:20803499-Cell Size,
pubmed-meshheading:20803499-Child,
pubmed-meshheading:20803499-Fatty Liver,
pubmed-meshheading:20803499-Female,
pubmed-meshheading:20803499-Gene Expression,
pubmed-meshheading:20803499-Gene Frequency,
pubmed-meshheading:20803499-Genotype,
pubmed-meshheading:20803499-Humans,
pubmed-meshheading:20803499-Lipase,
pubmed-meshheading:20803499-Liver,
pubmed-meshheading:20803499-Male,
pubmed-meshheading:20803499-Obesity,
pubmed-meshheading:20803499-Polymorphism, Single Nucleotide
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pubmed:year |
2010
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pubmed:articleTitle |
A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents.
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pubmed:affiliation |
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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