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Association of SSTR2 polymorphisms and glucose homeostasis phenotypes: the Insulin Resistance Atherosclerosis Family Study.

Sutton BS, Palmer ND, Langefeld CD, Xue B, Proctor A, Ziegler JT, Haffner SM, Norris JM, Bowden DW - Diabetes (2009)

Bottom Line: 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)(beta(homozygous) = -0.16; P(meta-analysis) = 0.0024-0.0030), decreased DI (beta(homozygous) = -0.35 to -5.16; P(meta-analysis) = 0.0075-0.027), and increased FBG (beta(homozygous) = 2.30; P(meta-analysis) = 0.045).SNPs outside the SSTR2-containing LD block were not associated with measures of glucose homeostasis.Thus, variants in SSTR2 may influence pathways of S(I)to modulate glucose homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

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)(beta(homozygous) = -0.16; P(meta-analysis) = 0.0024-0.0030), decreased DI (beta(homozygous) = -0.35 to -5.16; P(meta-analysis) = 0.0075-0.027), and increased FBG (beta(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.

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Haploview-generated LD map of the 10 SNPs at the SSTR2 locus in unrelated Hispanic Americans from the IRASFS. A: Regions of high LD (D′ = 1 and logarithm of odds [LOD] >2) are shown in the darkest shade. Markers with lower LD (0.45 < D′ < 1 and LOD >2) are shown in dark through light shades, with the color intensity decreasing with decreasing D′ value. Regions of low LD and low LOD scores (LOD <2) are shown in white. The number within each box indicates the D′ statistic value between the corresponding two SNPs. B: Regions of high correlation (r2 = 1) are shown in black. Markers with lower correlations (0 < r2 < 1) are shown in shades of gray with the color intensity decreasing with decreasing r2 value. Regions of low correlation (r2 = 0) are shown in white.
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Figure 1: Haploview-generated LD map of the 10 SNPs at the SSTR2 locus in unrelated Hispanic Americans from the IRASFS. A: Regions of high LD (D′ = 1 and logarithm of odds [LOD] >2) are shown in the darkest shade. Markers with lower LD (0.45 < D′ < 1 and LOD >2) are shown in dark through light shades, with the color intensity decreasing with decreasing D′ value. Regions of low LD and low LOD scores (LOD <2) are shown in white. The number within each box indicates the D′ statistic value between the corresponding two SNPs. B: Regions of high correlation (r2 = 1) are shown in black. Markers with lower correlations (0 < r2 < 1) are shown in shades of gray with the color intensity decreasing with decreasing r2 value. Regions of low correlation (r2 = 0) are shown in white.

Mentions: A total of 10 SNPs at the SSTR2 locus were genotyped on 1,425 Hispanic individuals. The majority of SNPs in this study had an MAF >0.15. Using the Haploview Tagger program, a subset of the genotyped SNPs (six SNPs genotyped in the HapMap Build 36 dataset) captured common variation (HapMap CEU, MAF >0.05, aggressive tagging algorithm) with a mean r2> 0.70. D′ values were high between SNPs within the SSTR2 gene (rs11077670, rs1868486, rs714925, rs998571, and rs7220818; D′ ≥0.8) and declined 5′ and 3′ to these markers (D′ <0.6;Fig. 1).


Association of SSTR2 polymorphisms and glucose homeostasis phenotypes: the Insulin Resistance Atherosclerosis Family Study.

Sutton BS, Palmer ND, Langefeld CD, Xue B, Proctor A, Ziegler JT, Haffner SM, Norris JM, Bowden DW - Diabetes (2009)

Haploview-generated LD map of the 10 SNPs at the SSTR2 locus in unrelated Hispanic Americans from the IRASFS. A: Regions of high LD (D′ = 1 and logarithm of odds [LOD] >2) are shown in the darkest shade. Markers with lower LD (0.45 < D′ < 1 and LOD >2) are shown in dark through light shades, with the color intensity decreasing with decreasing D′ value. Regions of low LD and low LOD scores (LOD <2) are shown in white. The number within each box indicates the D′ statistic value between the corresponding two SNPs. B: Regions of high correlation (r2 = 1) are shown in black. Markers with lower correlations (0 < r2 < 1) are shown in shades of gray with the color intensity decreasing with decreasing r2 value. Regions of low correlation (r2 = 0) are shown in white.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2682669&req=5

Figure 1: Haploview-generated LD map of the 10 SNPs at the SSTR2 locus in unrelated Hispanic Americans from the IRASFS. A: Regions of high LD (D′ = 1 and logarithm of odds [LOD] >2) are shown in the darkest shade. Markers with lower LD (0.45 < D′ < 1 and LOD >2) are shown in dark through light shades, with the color intensity decreasing with decreasing D′ value. Regions of low LD and low LOD scores (LOD <2) are shown in white. The number within each box indicates the D′ statistic value between the corresponding two SNPs. B: Regions of high correlation (r2 = 1) are shown in black. Markers with lower correlations (0 < r2 < 1) are shown in shades of gray with the color intensity decreasing with decreasing r2 value. Regions of low correlation (r2 = 0) are shown in white.
Mentions: A total of 10 SNPs at the SSTR2 locus were genotyped on 1,425 Hispanic individuals. The majority of SNPs in this study had an MAF >0.15. Using the Haploview Tagger program, a subset of the genotyped SNPs (six SNPs genotyped in the HapMap Build 36 dataset) captured common variation (HapMap CEU, MAF >0.05, aggressive tagging algorithm) with a mean r2> 0.70. D′ values were high between SNPs within the SSTR2 gene (rs11077670, rs1868486, rs714925, rs998571, and rs7220818; D′ ≥0.8) and declined 5′ and 3′ to these markers (D′ <0.6;Fig. 1).

Bottom Line: 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)(beta(homozygous) = -0.16; P(meta-analysis) = 0.0024-0.0030), decreased DI (beta(homozygous) = -0.35 to -5.16; P(meta-analysis) = 0.0075-0.027), and increased FBG (beta(homozygous) = 2.30; P(meta-analysis) = 0.045).SNPs outside the SSTR2-containing LD block were not associated with measures of glucose homeostasis.Thus, variants in SSTR2 may influence pathways of S(I)to modulate glucose homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

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)(beta(homozygous) = -0.16; P(meta-analysis) = 0.0024-0.0030), decreased DI (beta(homozygous) = -0.35 to -5.16; P(meta-analysis) = 0.0075-0.027), and increased FBG (beta(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.

Show MeSH
Related in: MedlinePlus