Article type: Research Article
Authors: Pivovarova, Olga; | Fisher, Eva | Dudziak, Katarzyna | Ilkavets, Iryna | Dooley, Steven | Slominsky, Petr | Limborska, Svetlana | Weickert, Martin
O.; ; | Spranger, Joachim; | Fritsche, Andreas | Boeing, Heiner | Pfeiffer, Andreas F.
H.; | Rudovich, Natalia;
Affiliations: Department of Clinical Nutrition, German Institute of
Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany | Department Endocrinology, Diabetes and Nutrition,
Charité University, Medicine, Campus Benjamin Franklin, Berlin,
Germany | Department of Epidemiology, German Institute of Human
Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany | Division of Endocrinology, Diabetology, Angiology,
Nephrology, and Clinical Chemistry, Department of Internal Medicine, University
Hospital, Tübingen and Eberhard Karls University Tübingen, Member of
the German, Center for Diabetes Research (DZD), Tübingen, Germany | Molecular Hepatology – Alcohol Associated Diseases,
Medical Clinic II, Faculty of Medicine Mannheim at Heidelberg University,
Mannheim, Germany | Institute of Molecular Genetics, Russian Academy of
Sciences, Moscow, Russia | Warwickshire Institute for the Study of Diabetes,
Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire,
Coventry, UK and Clinical Sciences Research Institute, Warwick Medical School,
University of Warwick, Coventry, UK
Note: [] Corresponding author: Dr. Olga Pivovarova, German Institute of
Human Nutrition Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal,
Germany. Tel.: +49 33 2008 8749; Fax: +49 33 2008 8777; E-mail: [email protected]
Abstract: Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM)
and related features including insulin secretion in various ethnic populations.
Connective tissue growth factor (CTGF) gene is an interesting T2DM candidate
gene in this chromosome region. CTGF is a key mediator of progressive
pancreatic fibrosis up-regulated in type 2 diabetes. In contrast, CTGF
inactivation in mice compromises islet cell proliferation during embryogenesis.
The aim of our study was to investigate an impact of CTGF genetic
variation on pancreatic beta-cell function and T2DM pathogenesis. We studied
the effect of a common CTGF polymorphism rs9493150 on the risk of the
T2DM development in three independent German cohorts. Specifically, the
association between CTGF polymorphism and non-invasive markers of
beta-cell area derived from oral glucose tolerance test was studied in subjects
without diabetes. Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO)
study (n=1026) (OR=0.637, CI (0.387–1.050); p=0.077) nor in the European Prospective
Investigation into Cancer and Nutrition-Potsdam (EPIC-Potsdam)
(n=3049) cohort (RR=0.77 CI
(0.49–1.20), p=0.249 for the recessive homozygote in
general model), a significant association with increased diabetes risk was
observed. The risk allele of rs9493150 had also no effect on markers of
beta-cell area in the combined analysis of the MESYBEPO and Tübingen Family
Study (n=1826). In conclusion, the polymorphism rs9493150
in the 5'-untranslated region of the CTGF gene has no association with
T2DM risk and surrogate markers of beta-cell area.
Keywords: Genetic association, connective tissue growth factor gene, C-peptide, blood glucose, beta-cell mass, type 2 diabetes mellitus
DOI: 10.3233/DMA-2011-0823
Journal: Disease Markers, vol. 31, no. 4, pp. 241-246, 2011
Received 14 October 2011
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Accepted 14 October 2011
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Published: 2011
