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Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts

In English

Författare

  • Anna Kotronen
  • Hannele Yki-Jarvinen
  • Anna Aminoff
  • Robert Bergholm
  • Kirsi H. Pietilainen
  • Jukka Westerbacka
  • Philippa J. Talmud
  • Steve E. Humphries
  • Anders Hamsten
  • Bo Isomaa
  • Leif Groop
  • Marju Orho-Melander
  • Ewa Ehrenborg
  • Rachel M. Fisher
Visa allt

Summary, in English

Aims: We investigated whether polymorph isms in candidate genes involved in lipid metabolism and type 2 diabetes are related to liver I, at content. Methods: Liver fat content was measured using proton magnetic resonance spectroscopy (H-1-MRS) in 302 Finns, in whom single nucleotide polymorphisms (SNPs) in acyl-CoA synthetase long-chain family member 4 (ACSL4). acliponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2), and the three peroxisome proliferator-activated receptors (PPARA, PPARD, and PPARG) were analyzed. To validate our findings, SNPs significantly associated with liver fat content were Studied in two independent cohorts and related to surrogate markers of liver fat content. Results: In the Finnish subjects, polymorphisms in ACSL4 (rs7887981), ADIPOR2 (rs767870), and PPARG (rs3856806) were significantly associated with liver fat content measured with H-1-MRS after adjusting for age, gender, and BMI, Anthropometric and circulating parameters were comparable between genotypes. In the first validation cohort of similar to 600 Swedish men, ACSL4 rs7887981 was related to fasting insulin and triglyceride concentrations, and ADIPOR2 rs767870 to serum gamma glutamyltransfer concentrations after adjusting for BMI. The SNP in PPARG (rs3856806) was not significantly associated with any relevant metabolic parameter in this cohort. In the second validation cohort of similar to 3000 subjects from Western Finland, ADIPOR2 rs767870, but not ACSL4 rs7887981 was related to fasting triglyceride concentrations. Conclusions: Genetic variation, particularly in the ADIPOR2 gene, contributes to variation in hepatic fat accumulation in humans.

Publiceringsår

2009

Språk

Engelska

Sidor

593-602

Publikation/Tidskrift/Serie

European Journal of Endocrinology

Volym

160

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Society of the European Journal of Endocrinology

Ämne

  • Endocrinology and Diabetes

Status

Published

Forskningsgrupp

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Övrigt

  • ISSN: 1479-683X