The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3

American Journal of Human Genetics
Haruhiko OsawaHideichi Makino

Abstract

Insulin resistance is a major cause of type 2 diabetes mellitus (T2DM). Resistin, an adipocyte-secreted hormone, antagonizes insulin. Transgenic mice that overexpress the resistin gene (Retn) in adipose tissue are insulin-resistant, whereas Retn (-/-) mice show lower fasting blood glucose, suggesting that the altered Retn promoter function could cause diabetes. To determine the role of RETN in human T2DM, we analyzed polymorphisms in its 5' flanking region. We found that the -420G/G genotype was associated with T2DM (397 cases and 406 controls) (P=.008; adjusted odds ratio = 1.97 [by logistic regression analysis]) and could accelerate the onset of disease by 4.9 years (P=.006 [by multiple regression analysis]). Meta-analysis of 1,888 cases and 1,648 controls confirmed this association (P=.013). Linkage disequilibrium analysis revealed that the -420G/G genotype itself was a primary variant determining T2DM susceptibility. Functionally, Sp1 and Sp3 transcription factors bound specifically to the susceptible DNA element that included -420G. Overexpression of Sp1 or Sp3 enhanced RETN promoter activity with -420G in Drosophila Schneider line 2 cells that lacked endogenous Sp family members. Consistent with these findings, fasting se...Continue Reading

References

Mar 1, 1992·Diabetes Care·R A DeFronzoE Ferrannini
Dec 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·P P Di Nocera, I B Dawid
Oct 25, 1996·Science·E S Lander
Feb 12, 1998·Annals of Internal Medicine·J LauC H Schmid
Jun 8, 2000·Bioinformatics·G R Abecasis, W O Cookson
Jul 11, 2001·Biochemical and Biophysical Research Communications·I Nagaev, U Smith
Apr 30, 2002·Diabetes·James C EngertThomas J Hudson
Jul 12, 2002·American Journal of Physiology. Endocrinology and Metabolism·Mark I McCarthy, Philippe Froguel
Sep 6, 2002·The Journal of Clinical Endocrinology and Metabolism·Xiaowei MaAlessandro Doria
Oct 2, 2002·Molecular and Cellular Endocrinology·Peter Bouwman, Sjaak Philipsen
Dec 28, 2002·Diabetes Care·UNKNOWN Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
Dec 31, 2002·American Journal of Human Genetics·Kazuya OmiKatsushi Tokunaga
Aug 29, 2003·The Journal of Biological Chemistry·Michal PravenecTheodore W Kurtz
Dec 23, 2003·Clinica Chimica Acta; International Journal of Clinical Chemistry·Aya FujinamiMitsuhiro Ohta
Feb 21, 2004·Science·Ronadip R BanerjeeMitchell A Lazar
Mar 31, 2004·Journal of Internal Medicine·Claire M Steppan, Mitchell A Lazar
May 25, 2004·Science·Saurabh D PatelLawrence Shapiro

❮ Previous
Next ❯

Citations

Dec 16, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·José López-MirandaFrancisco Pérez-Jiménez
Nov 3, 2009·Diabetologia·C Menzaghi, V Trischitta
Aug 19, 2006·Journal of Human Genetics·Yasunori SatoKimio Yoshimura
Jan 12, 2008·Clinical and Experimental Medicine·H KoçakH Işsever
May 1, 2008·Current Diabetes Reports·Stéphane Cauchi, Philippe Froguel
Oct 2, 2012·Genetic Testing and Molecular Biomarkers·Imen BoumaizaAli Bouslama
Aug 8, 2012·Metabolic Syndrome and Related Disorders·Ryuichi KawamotoTetsuro Miki
Aug 2, 2008·AIDS·Koustubh RanadeMichael P Dube
Feb 18, 2011·Annals of Human Genetics·Cia-Hin Lau, Sekaran Muniandy
Mar 3, 2007·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Margarita Terán-García, Claude Bouchard
Feb 4, 2009·The Journal of Clinical Investigation·Mohammed QatananiMitchell A Lazar
Dec 23, 2008·Journal of Perinatal Medicine·Shali Mazaki-ToviPooja Mittal
Jun 18, 2009·Journal of Perinatal Medicine·Shali Mazaki-ToviJuan Pedro Kusanovic
Feb 3, 2007·Journal of Zhejiang University. Science. B·Yun-mei YangWei-dong Huang
Nov 15, 2008·Molecular Medicine·Katja RabeUli C Broedl
Jan 30, 2009·Journal of Clinical Biochemistry and Nutrition·Kanjana SuriyapromRungsunn Tungtrongchitr
Nov 24, 2011·Experimental Diabetes Research·Mi-Young KimYong Ho Ahn
Jun 23, 2009·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Tsuyoshi BabaTsuyoshi Saito
Aug 17, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Pilar Codoñer-Franch, Eulalia Alonso-Iglesias
Apr 19, 2011·Trends in Endocrinology and Metabolism : TEM·Daniel R Schwartz, Mitchell A Lazar
Feb 23, 2010·Translational Research : the Journal of Laboratory and Clinical Medicine·Sabir HussainQamar Javed
Sep 3, 2009·Molecular and Cellular Endocrinology·Sandra GalicGregory R Steinberg
May 1, 2009·Obesity Research & Clinical Practice·Yoshihiro MiyamotoTakayuki Morisaki
Oct 22, 2008·Trends in Endocrinology and Metabolism : TEM·Tarik Issad, Meishiue Kuo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biomarkers for Type 2 Diabetes

Biomarkers can help understand chronic diseases and assist in risk prediction for prevention and early detection of diseases. Here is the latest research on biomarkers in type 2 diabetes, a disease in which the body is unable to produce or properly use insulin.