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,CTGFinactivation in mice compromises islet cell proliferation during embryogenesis. The aim of our study was to investigate an impact ofCTGFgenetic variation on pancreatic beta-cell function and T2DM pathogenesis. We studied the effect of a commonCTGFpolymorphism rs9493150 on the risk of the T2DM development in three independent German cohorts. Specifically, the association betweenCTGFpolymorphism 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 theCTGFgene has no association with T2DM risk and surrogate markers of beta-cell area.
Highlights
Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations
We investigated the association of a common Connective tissue growth factor (CTGF) polymorphism on diabetes risk in the prospective casecohort study of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort and in an independent cross-sectional Metabolic Syndrome Berlin Potsdam (MESYBEPO) study from the same geographical region of Germany
We examined whether CTGF polymorphism rs9493150 is associated with variations in the Cpeptide–to– glucose ratio which was used in our study as non-invasive marker of pancreatic beta-cell area
Summary
Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations. 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. Connective tissue growth factor impaired fasting glucose impaired glucose tolerance Metabolic Syndrome BerlinPotsdam study normal glucose tolerance oral glucose tolerance test odds ratio single nucleotide polymorphism type 2 diabetes mellitus Tubingen Family Study. We investigated the association of a common CTGF polymorphism on diabetes risk in the prospective casecohort study of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort and in an independent cross-sectional Metabolic Syndrome Berlin Potsdam (MESYBEPO) study from the same geographical region of Germany. The association between the CTGF polymorphism and noninvasive markers of beta-cell area derived from oral glucose tolerance test [16] was investigated in both MESYBEPO and in Tubingen Family Study (TU F Study). Ectonucleotide pyrophosphatase phosphodiesterase (ENPP1) is a well characterized positional candidate gene for T2DM at chromosome 6q23 identified in a number of whole-genome association studies [4,5,6]
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