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Comment
. 2013 Sep;62(9):3019-21.
doi: 10.2337/db13-0871.

Pharmacogenetic perturbations in humans as a tool to generate mechanistic insight

Jose C Florez  1
Affiliations
Comment

Pharmacogenetic perturbations in humans as a tool to generate mechanistic insight

Jose C Florez. Diabetes. 2013 Sep.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Diagram depicting the model postulated by the findings in ‘t Hart et al. (7). The G allele at rs7202877 near the CTRB1 and CTRB2 genes raises their expression levels, resulting in higher chymotrypsin activity. Through unclear processes, this improves sensitivity of pancreatic β-cells to the action of GLP-1 while diminishing the individual’s sensitivity to DPP-4. Increased incretin sensitivity improves β-cell function (13), thereby lowering T2D risk (10). Because G-allele carriers are less sensitive to DPP-4, they might benefit less from DPP-4 inhibition. In addition, the G allele has been associated with type 1 diabetes (T1D) (11). Hashed arrows indicate steps in the model where mechanistic insight remains speculative (see text for details).
See this image and copyright information in PMC

Comment on

  • The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway.
    't Hart LM, Fritsche A, Nijpels G, van Leeuwen N, Donnelly LA, Dekker JM, Alssema M, Fadista J, Carlotti F, Gjesing AP, Palmer CN, van Haeften TW, Herzberg-Schäfer SA, Simonis-Bik AM, Houwing-Duistermaat JJ, Helmer Q, Deelen J, Guigas B, Hansen T, Machicao F, Willemsen G, Heine RJ, Kramer MH, Holst JJ, de Koning EJ, Häring HU, Pedersen O, Groop L, de Geus EJ, Slagboom PE, Boomsma DI, Eekhoff EM, Pearson ER, Diamant M. 't Hart LM, et al. Diabetes. 2013 Sep;62(9):3275-81. doi: 10.2337/db13-0227. Epub 2013 May 14. Diabetes. 2013. PMID: 23674605 Free PMC article. Clinical Trial.

References

    1. Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science 2008;322:881–888 - PMC - PubMed
    1. Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med 2010;363:166–176 - PubMed
    1. Billings LK, Florez JC. The genetics of type 2 diabetes: what have we learned from GWAS? Ann N Y Acad Sci 2010;1212:59–77 - PMC - PubMed
    1. McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med 2010;363:2339–2350 - PubMed
    1. Hirschhorn JN. Genomewide association studies—illuminating biologic pathways. N Engl J Med 2009;360:1699–1701 - PubMed

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