Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes: The Insulin Resistance Atherosclerosis Family Study

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.