title: A polymorphism within the connective tissue growth factor (CTGF) gene has no effect on non-invasive markers of beta-cell area and risk of type 2 diabetes.
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.
authors: Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal. olga.pivovarova@dife.de
authors: Olga
authors: O
authors: Pivovarova
authors: Eva
authors: E
authors: Fisher
authors: Katarzyna
authors: K
authors: Dudziak
authors: Iryna
authors: I
authors: Ilkavets
authors: Steven
authors: S
authors: Dooley
authors: Petr
authors: P
authors: Slominsky
authors: Svetlana
authors: S
authors: Limborska
authors: Martin O
authors: MO
authors: Weickert
authors: Joachim
authors: J
authors: Spranger
authors: Andreas
authors: A
authors: Fritsche
authors: Heiner
authors: H
authors: Boeing
authors: Andreas F H
authors: AF
authors: Pfeiffer
authors: Natalia
authors: N
authors: Rudovich
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D015331:Cohort Studies; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D005838:Genotype; D005858:Germany; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; C526317:CCN2 protein, human; D005819:Genetic Markers; D055513:Connective Tissue Growth Factor