Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes: The IRAS Family Study

Abstract

Aim. This study evaluated the influence of somatostatin receptor 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRAS-FS). SSTR2 is a G protein-coupled receptor which, in response to somatostatin, mediates inhibition of insulin, glucagon and growth hormone release, and thus may affect glucose homeostasis.

Methods. Ten SNPs spanning the gene were chosen using a SNP density selection algorithm and genotyped on 1425 Hispanic-American individuals from 90 families in the IRAS-FS. 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 glucose (GFAST) using generalized estimating equations (GEE1).

Results. The SSTR2 locus was encompassed by a single LD block (D'=0.91-1.00, r²=0.09-0.97) which 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 GFAST (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 insulin sensitivity to modulate glucose homeostasis.