Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

• Published in: Diabetes (New York, N.Y.) Vol. 58; no. 6; pp. 1457 - 1462
• Main Authors: Sutton, Beth S., Palmer, Nicholette D., Langefeld, Carl D., Xue, Bingzhong, Proctor, Alexandria, Ziegler, Julie T., Haffner, Steven M., Norris, Jill M., Bowden, Donald W.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.06.2009
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db08-0189

Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes The Insulin Resistance Atherosclerosis Family Study Beth S. Sutton 1 , 2 , Nicholette D. Palmer 1 , 2 , Carl D. Langefeld 3 , Bingzhong Xue 2 , Alexandria Proctor 1 , 2 , Julie T. Ziegler 3 , Steven M. Haffner 4 , Jill M. Norris 5 and Donald W. Bowden 1 , 2 , 6 1 Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina; 2 Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina; 3 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina; 4 Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas; 5 Department of Preventive Medicine and Biometrics, University of Colorado Denver, Denver, Colorado; 6 Department of Internal Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas. Corresponding author: Donald W. Bowden, dbowden{at}wfubmc.edu . B.S.S. and N.D.P. contributed equally to this study. Abstract OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 ( SSTR2 ) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein–coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP density selection algorithm and genotyped on 1,425 Hispanic-American individuals from 90 families in the IRASFS. These families comprised two samples (set 1 and set 2), which were analyzed individually and as a combined set. Single SNP tests of association were performed for four glucose homeostasis measures—insulin sensitivity (S I ), acute insulin response (AIR), disposition index (DI), and fasting blood glucose (FBG)—using generalized estimating equations. RESULTS The SSTR2 locus was encompassed by a single linkage disequilibrium (LD) block (D′ = 0.91–1.00; r 2 = 0.09–0.97) that contained four of the ten SNPs evaluated. Within the SSTR2 -containing LD block, evidence of association was observed in each of the two sets and in a combined analysis with decreased S I (β homozygous = −0.16; P meta-analysis = 0.0024–0.0030), decreased DI (β homozygous = −0.35 to −5.16; P meta-analysis = 0.0075–0.027), and increased FBG (β homozygous = 2.30; P meta-analysis = 0.045). SNPs outside the SSTR2 -containing LD block were not associated with measures of glucose homeostasis. CONCLUSIONS We observed evidence for association of SSTR2 polymorphisms with measures of glucose homeostasis. Thus, variants in SSTR2 may influence pathways of S I to modulate glucose homeostasis. 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. Received February 11, 2008. Accepted March 12, 2009. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. © 2009 by the American Diabetes Association.