Diabetologie und Stoffwechsel 2010; 5 - P79
DOI: 10.1055/s-0030-1253807

Polymorphism within connective tissue growth factor (CTGF) gene strongly predicts the marker of the ß-cell mass in non diabetic subjects

O Pivovarova 1, 2, E Fisher 3, MO Weickert 4, 5, H Boeing 3, AFH Pfeiffer 1, 2, N Rudovich 1, 2
  • 1Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke, Klinische Ernährung, Nuthetal, Germany
  • 2Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Endokrinologie, Diabetes und Ernährungsmedizin, Berlin, Germany
  • 3Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke, Epidemiologie, Nuthetal, Germany
  • 4Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
  • 5Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, United Kingdom

Aims: Connective tissue growth factor (CTGF) is a key determinant of progressive pancreas fibrosis and is up-regulated in Type 2 diabetes mellitus (T2DM). Recent studies indicate that CTGF promotes fibrogenesis both by enhancing pancreatic stellate cells proliferation and by releasing proinflammatory cytokines. CTGF inactivation in mice compromises islet cell proliferation during embryogenesis.

Methods: We investigated the effect of a common polymorphism rs9493150 located in the CTGF locus on diabetes risk in two independent German cohorts from the same geographical region. The association between CTGF polymorphism and a non-invasive marker of beta-cell mass, C-peptide to glucose ratio, was additionally investigated.

Results: Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) cohort (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 general model) we found a significant association with increased diabetes risk. The C-allele of rs9493150 was strongly associated with decreased C-peptide to glucose ratio at 0 and 30 minutes of the oral glucose load in the general MESYBEPO cohort, both when investigating all participants (n=886; p=0.005 and p=0.004, respectively) and the subcohort of non-diabetic subjects (n=739; p=0.004 and p=0.024, respectively).

Conclusions: These results indicate that the polymorphism in 3′-region of CTGF gene strongly predicts a surrogate marker of beta cell mass in non-diabetic subjects, although no association with T2DM risk was found in two independent cohorts.