Details

Autor(en) / Beteiligte

• TRAURIG, Michael T
• PERMANA, Paska A
• NAIR, Saraswathy
• KOBES, Sayuko
• BOGARDUS, Clifton
• BAIER, Leslie J

Titel

Differential Expression of Matrix Metalloproteinase 3 (MMP3) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians

Ist Teil von

• Diabetes (New York, N.Y.), 2006-11, Vol.55 (11), p.3160-3165

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2006

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Differential Expression of Matrix Metalloproteinase 3 ( MMP3 ) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians Michael T. Traurig , Paska A. Permana , Saraswathy Nair , Sayuko Kobes , Clifton Bogardus and Leslie J. Baier From the Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona Address correspondence and reprint requests to Leslie J. Baier, PhD, NIDDK, NIH, 445 North 5th St., Phoenix, AZ 85004. E-mail: lbaier{at}phx.niddk.nih.gov Abstract Prior microarray studies comparing global gene expression patterns in preadipocytes/stromal vascular cells isolated from nonobese nondiabetic versus obese nondiabetic Pima Indians showed that matrix metalloproteinase 9 ( MMP9 ) is upregulated in obese subjects. The current study targeted analysis of nine additional MMP genes that cluster to a region on chromosome 11q22 that is linked to BMI and percent body fat. Differential-display PCR showed that MMP3 is downregulated in preadipocytes/stromal vascular cells from obese subjects, and real-time PCR showed that MMP3 expression levels are negatively correlated with percent body fat. To determine whether variants within MMP3 are responsible for its altered expression, MMP3 was sequenced, and seven representative variants were genotyped in 1,037 Pima subjects for association analyses. Two variants were associated with both BMI and type 2 diabetes, and two additional variants were associated with type 2 diabetes alone; however, none of these variants were associated with MMP3 expression levels. We propose that the MMP3 pathway is altered in human obesity, but this alteration may be the result of a combination of genetic variation within the MMP3 locus itself, as well as variation in additional factors, either primary or secondary to obesity, that regulate expression of the MMP3 gene. GAPDH, glyceraldehyde-3-phosphate dehydrogenase MMP, matrix metalloproteinase SNP, single nucleotide polymorphism UTR, untranslated region Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted July 31, 2006. Received March 21, 2006. DIABETES