BACKGROUND: The peroxisome proliferator activated receptor-gamma (PPARG) is a nuclear receptor that regulates adipocyte differentiation, insulin sensitivity and lipid metabolism, thus, it represents a good candidate gene for non-alcoholic fatty liver disease (NAFLD). PURPOSE AND METHOD: We investigated the association of two PPARG variants (Pro12Ala and C1431T) with NAFLD and its histological features. DNA was extracted from 274 archived, formalin-fixed liver biopsy specimens from 212 patients with NAFLD and 62 controls with normal liver histology. RESULTS: Individual SNPs did not show significant association with NAFLD or its histological features. A haplotype comprised of both minor alleles (GT) was less enriched whereas a haplotype comprised of the two major alleles (CC) was more enriched in subjects with NAFLD compared to controls [9.3% vs. 28.1% for GT (P = 0.001, OR 0.26 (range 0.14-0.48) and 80.4% vs. 64.8% for CC (P = 0.037, OR 2.23 (range 1.30-3.81)]. Both haplotypes were significantly associated with steatosis and fibrosis. The GT haplotype was also associated with lobular inflammation. CONCLUSIONS: Genetic variation in PPARG is associated with NAFLD, and the GT haplotype is associated with inflammatory and fibrotic changes that denote histologically advanced NAFLD.
BACKGROUND: The peroxisome proliferator activated receptor-gamma (PPARG) is a nuclear receptor that regulates adipocyte differentiation, insulin sensitivity and lipid metabolism, thus, it represents a good candidate gene for non-alcoholic fatty liver disease (NAFLD). PURPOSE AND METHOD: We investigated the association of two PPARG variants (Pro12Ala and C1431T) with NAFLD and its histological features. DNA was extracted from 274 archived, formalin-fixed liver biopsy specimens from 212 patients with NAFLD and 62 controls with normal liver histology. RESULTS: Individual SNPs did not show significant association with NAFLD or its histological features. A haplotype comprised of both minor alleles (GT) was less enriched whereas a haplotype comprised of the two major alleles (CC) was more enriched in subjects with NAFLD compared to controls [9.3% vs. 28.1% for GT (P = 0.001, OR 0.26 (range 0.14-0.48) and 80.4% vs. 64.8% for CC (P = 0.037, OR 2.23 (range 1.30-3.81)]. Both haplotypes were significantly associated with steatosis and fibrosis. The GT haplotype was also associated with lobular inflammation. CONCLUSIONS: Genetic variation in PPARG is associated with NAFLD, and the GT haplotype is associated with inflammatory and fibrotic changes that denote histologically advanced NAFLD.
Authors: David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal Journal: Hepatology Date: 2005-06 Impact factor: 17.425
Authors: Jason M Hui; James G Kench; Shivakumar Chitturi; Archana Sud; Geoffrey C Farrell; Karen Byth; Pauline Hall; Mahbub Khan; Jacob George Journal: Hepatology Date: 2003-08 Impact factor: 17.425
Authors: S S Deeb; L Fajas; M Nemoto; J Pihlajamäki; L Mykkänen; J Kuusisto; M Laakso; W Fujimoto; J Auwerx Journal: Nat Genet Date: 1998-11 Impact factor: 38.330
Authors: A Kotronen; L E Johansson; L M Johansson; C Roos; J Westerbacka; A Hamsten; R Bergholm; P Arkkila; J Arola; T Kiviluoto; R M Fisher; E Ehrenborg; M Orho-Melander; M Ridderstråle; L Groop; H Yki-Järvinen Journal: Diabetologia Date: 2009-02-18 Impact factor: 10.122