Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

The Insulin Resistance Atherosclerosis Family Study

  1. Beth S. Sutton1,2,
  2. Nicholette D. Palmer1,2,
  3. Carl D. Langefeld3,
  4. Bingzhong Xue2,
  5. Alexandria Proctor1,2,
  6. Julie T. Ziegler3,
  7. Steven M. Haffner4,
  8. Jill M. Norris5 and
  9. Donald W. Bowden1,2,6
  1. 1Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina;
  2. 2Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina;
  3. 3Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina;
  4. 4Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas;
  5. 5Department of Preventive Medicine and Biometrics, University of Colorado Denver, Denver, Colorado;
  6. 6Department of Internal Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas.
  1. Corresponding author: Donald W. Bowden, dbowden{at}wfubmc.edu.

  1. 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 (SI), 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; r2 = 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 SI(βhomozygous = −0.16; Pmeta-analysis = 0.0024–0.0030), decreased DI (βhomozygous = −0.35 to −5.16; Pmeta-analysis = 0.0075–0.027), and increased FBG (βhomozygous = 2.30; Pmeta-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 SIto 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.

« Previous | Next Article »Table of Contents

This Article

  1. Published online before print March 26, 2009, doi: 10.2337/db08-0189 Diabetes June 2009 vol. 58 no. 6 1457-1462
  1. Free via Creative Commons: CC
  2. » Abstract
  3. Full Text
  4. Full Text (PDF)
  5. Online-Only Appendix
  6. All Versions of this Article:
    1. db08-0189v1
    2. 58/6/1457 most recent

Current Issue

  1. November 2009, 58 (11)
    Current Issue
  1. Alert me to new issues of Diabetes