Z Gastroenterol 2011; 49 - P426
DOI: 10.1055/s-0031-1285697

Common FOXO1 variant, a risk factor for impaired glucose tolerance and diabetes, in gallstone patients: Analysis of three independent cohorts

M Krawczyk 1, R Schirin-Sokhan 2, M Mahler 1, H Molina 3, L Azocar 3, M Acalovschi 4, JF Miquel 3, F Lammert 1
  • 1Saarland University Hospital, Department of Medicine II, Homburg, Germany
  • 2Department of Medicine III, Aachen University Hospital, Aachen, Germany
  • 3Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiagoe de Chile, Chile
  • 4Department of Medicine III, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

Background: Gallstones (GS) develop frequently in individuals with metabolic syndrome. Of note, forkhead transcription factor (FOXO1) regulates the hepatobiliary cholesterol secretion leading to GS [1], and the FOXO1 variant (rs2721068) increases the diabetes risk [2]. Here, we combine case-control and sib-pairs analyses and investigate the FOXO1 polymorphism in gallstone patients.

Methods: We analyzed three independent cohorts from German (184 patients with GS and 184 controls), Romania (234 sibs with GS from 107 families and 260 controls), and Chile (485 patients and 229 controls). The FOXO1 polymorphism rs2721068 was genotyped using a PCR-based assay with 5'-nuclease and fluorescence detection. Non-parametric linkage (NPL) analysis and case-control association tests were performed.

Results: Romanian [CC] individuals showed significantly increased cholesterol serum levels as compared to carries of the [T] allele (253.9±50.2 vs. 222.3±47.2mg/dL, P=0.006). In contrast to other studies [2], this polymorphism was not associated with serum glucose levels or HOMA indices in any cohort (all P>0.05). Neither genotype distributions (P>0.05) nor NPL scores (NPL=-0.042) provided evidence for association or linkage between the FOXO1 variant and gallstones in Germans (common OR=1.33, P=0.08), Romanians (OR=1.05), or Chileans (OR=1.12), or in NAFLD individuals (all P>0.05).

Conclusions: The FOXO1 polymorphism does neither increase the risk of gallstones in individuals with NAFLD nor in general but may be associated with metabolic traits. [1] Biddinger et al. Nat Med 2008

[2] Müssig et al. J Clin Endocrinol Metab 2009