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A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans

Kotronen, A. ; Johansson, L. E. ; Johansson, L. M. ; Roos, C. ; Westerbacka, J. ; Hamsten, A. ; Bergholm, R. ; Arkkila, P. ; Arola, J. and Kiviluoto, T. , et al. (2009) In Diabetologia 52(6). p.1056-1060
Abstract
It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin... (More)
It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin sensitivities were measured using a euglycaemic-hyperinsulinaemic (insulin infusion 0.3 mU kg(-1) min(-1)) clamp technique combined with infusion of [3-H-3]glucose in 109 participants. The rs738409 G allele in PNPLA3 was associated with increased quantitative measures of liver fat content (p = 0.011) and serum aspartate aminotransferase concentrations (p = 0.002) independently of age, sex and BMI. Fasting serum insulin and hepatic and adipose tissue insulin sensitivity were related to liver fat content independently of genotype status. PNPLA3 mRNA expression in the liver was positively related to obesity (r = 0.62, p < 0.0001) and to liver fat content (r = 0.58, p = 0.025) in participants who were not morbidly obese (BMI < 40 kg/m(2)). A common variant in PNPLA3 increases the risk of hepatic steatosis in humans. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Non-alcoholic fatty liver, disease, rs738409, Liver enzymes, Hepatic insulin sensitivity, Gene expression, Adiponutrin, Adipose tissue insulin sensitivity
in
Diabetologia
volume
52
issue
6
pages
1056 - 1060
publisher
Springer
external identifiers
  • wos:000265684500011
  • scopus:67349174005
ISSN
1432-0428
DOI
10.1007/s00125-009-1285-z
language
English
LU publication?
yes
id
89577a1d-9226-457b-adfd-e3110bd57d0a (old id 1428003)
date added to LUP
2016-04-01 12:35:27
date last changed
2022-02-11 17:00:52
@article{89577a1d-9226-457b-adfd-e3110bd57d0a,
  abstract     = {{It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin sensitivities were measured using a euglycaemic-hyperinsulinaemic (insulin infusion 0.3 mU kg(-1) min(-1)) clamp technique combined with infusion of [3-H-3]glucose in 109 participants. The rs738409 G allele in PNPLA3 was associated with increased quantitative measures of liver fat content (p = 0.011) and serum aspartate aminotransferase concentrations (p = 0.002) independently of age, sex and BMI. Fasting serum insulin and hepatic and adipose tissue insulin sensitivity were related to liver fat content independently of genotype status. PNPLA3 mRNA expression in the liver was positively related to obesity (r = 0.62, p &lt; 0.0001) and to liver fat content (r = 0.58, p = 0.025) in participants who were not morbidly obese (BMI &lt; 40 kg/m(2)). A common variant in PNPLA3 increases the risk of hepatic steatosis in humans.}},
  author       = {{Kotronen, A. and Johansson, L. E. and Johansson, L. M. and Roos, C. and Westerbacka, J. and Hamsten, A. and Bergholm, R. and Arkkila, P. and Arola, J. and Kiviluoto, T. and Fisher, R. M. and Ehrenborg, E. and Orho-Melander, Marju and Ridderstråle, Martin and Groop, Leif and Yki-Jarvinen, H.}},
  issn         = {{1432-0428}},
  keywords     = {{Non-alcoholic fatty liver; disease; rs738409; Liver enzymes; Hepatic insulin sensitivity; Gene expression; Adiponutrin; Adipose tissue insulin sensitivity}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1056--1060}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans}},
  url          = {{http://dx.doi.org/10.1007/s00125-009-1285-z}},
  doi          = {{10.1007/s00125-009-1285-z}},
  volume       = {{52}},
  year         = {{2009}},
}