PNPLA3 Gene-by-Visceral Adipose Tissue Volume Interaction and the Pathogenesis of Fatty Liver Disease: The NHLBI Family Heart Study

Graff, Mariaelisa; North, Kari E.; Franceschini, Nora; Reiner, Alexander P.; Feitosa, Mary F.; Carr, John Jeffrey; Gordon-Larsen, Penny; Wojczynski, Mary K.; & Borecki, Ingrid B. (Forthcoming). PNPLA3 Gene-by-Visceral Adipose Tissue Volume Interaction and the Pathogenesis of Fatty Liver Disease: The NHLBI Family Heart Study. International Journal of Obesity. PMCID: PMC3410967

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Journal Article

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Author(s):
Graff, Mariaelisa
North, Kari E.
Franceschini, Nora
Reiner, Alexander P.
Feitosa, Mary F.
Carr, John Jeffrey
Gordon-Larsen, Penny
Wojczynski, Mary K.
Borecki, Ingrid B.

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Forthcoming

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International Journal of Obesity

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DOI:
10.1038/ijo.2012.65

PMCID:
PMC3410967

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Reference ID:
5300

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Abstract:

BACKGROUND:Fatty liver disease (FLD) is characterized by increased intrahepatic triglyceride content with or without inflammation and is associated with obesity, and features of the metabolic syndrome. Several recent genome-wide association studies have reported an association between single-nucleotide polymorphism rs738409 in the (patatin-like phospholipase domain-containing protein 3) PNPLA3 gene and FLD. Liver attenuation (LA; hounsfield units, HU) by computed tomography is a non-invasive measure of liver fat, with lower values of HU indicating higher liver fat content. Clinically, a LA value of <0.01). The interaction of 100 cm(3) VAT and the variant allele was associated with a greater decrease in LA in women than men (-4.8+/-0.6 and -2.2+/-0.5 HU, respectively).CONCLUSIONS:The interaction between genotype and VAT volume suggest key differences in the role of PNPLA3 genotype in conjunction with abdominal VAT in liver fat accrual. The stronger association of the PNPLA3 genotype and liver fat in women suggests that women may be more sensitive to liver fat accumulation in the setting of increased visceral fat, compared with men. The presence of the PNPLA3 variant genotype, particularly in the context of high VAT content may have an important role in FLD.International Journal of Obesity advance online publication, 1 May 2012; doi:10.1038/ijo.2012.65.

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http://dx.doi.org/10.1038/ijo.2012.65

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Graff, Mariaelisa; North, Kari E.; Franceschini, Nora; Reiner, Alexander P.; Feitosa, Mary F.; Carr, John Jeffrey; Gordon-Larsen, Penny; Wojczynski, Mary K.; & Borecki, Ingrid B. (Forthcoming). PNPLA3 Gene-by-Visceral Adipose Tissue Volume Interaction and the Pathogenesis of Fatty Liver Disease: The NHLBI Family Heart Study. International Journal of Obesity. PMCID: PMC3410967