Dataset Information

Polymorphisms in the SOCS7 gene and glucose homeostasis traits.

ABSTRACT: SOCS7 is a member of the suppressor of cytokine signaling family of proteins and is expressed in skeletal muscle and islets. SOCS7 deficient mice develop islet hyperplasia in the setting of increased insulin sensitivity and normal glucose tolerance. The objective of this study was to determine if variants in SOCS7 play a role in variation of glucose and insulin levels and the development of type 2 diabetes (T2DM).Five SOCS7 tagging SNPs were genotyped in diabetic and nondiabetic Old Order Amish. A case-control study was performed in T2DM (n?=?145) and normal glucose tolerant (n?=?358) subjects. Nominal associations were observed with T2DM and the minor alleles for rs8068600 (P?=?0.01) and rs8074124 (P?=?0.04); however, only rs8068600 remained significant after Bonferroni adjustment for multiple comparisons (P?=?0.01). Among nondiabetic Amish (n?=?765), no significant associations with glucose or insulin traits including fasting or 2 hour glucose and insulin from the oral glucose tolerance test, insulin or glucose area under the curve, Matsuda Index or HOMA-IR were found for any of the SNPs.In conclusion, genetic variants in the SOCS7 gene do not impact variation in glucose homeostasis traits and only minimally impact risk of T2DM in the Old Order Amish. Our study was not able to address whether rare variants that potentially impact gene function might influence T2DM risk.

SUBMITTER: Capuano MM

PROVIDER: S-EPMC3686602 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Polymorphisms in the SOCS7 gene and glucose homeostasis traits.

Capuano Melissa M MM Sorkin John D JD Chang Yen-Pei C YP Ling Hua H O'Connell Jeffrey R JR Rothman Paul B PB Mitchell Braxton D BD Silver Kristi D KD

BMC research notes 20130615

<h4>Background</h4>SOCS7 is a member of the suppressor of cytokine signaling family of proteins and is expressed in skeletal muscle and islets. SOCS7 deficient mice develop islet hyperplasia in the setting of increased insulin sensitivity and normal glucose tolerance. The objective of this study was to determine if variants in SOCS7 play a role in variation of glucose and insulin levels and the development of type 2 diabetes (T2DM).<h4>Results</h4>Five SOCS7 tagging SNPs were genotyped in diabet ...[more]

PMID: 23767996

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Project description:The SOCS3 gene product participates in the feedback inhibition of a range of cytokine signals. Most notably, SOCS3 inhibits the functioning of leptin and downstream steps in insulin signaling after being expressed by terminal transcription factors, such as STAT3 and c-fos. The SOCS3 gene is located in the chromosome region 17q24-17q25, previously linked to body mass index (BMI), visceral adipose tissue (VAT), and waist circumference (WAIST) in Hispanic families in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A high density map of 1,536 single nucleotide polymorphisms (SNPs) was constructed to cover a portion of the 17q linkage interval in 1,425 Hispanic subjects from 90 extended families in IRASFS. Analysis of this dense SNP map data revealed evidence of association of rs9914220 (located 10 kb 5' of the SOCS3 gene) with BMI, VAT, and WAIST (P-value ranging from 0.003 to 0.017). Using a tagging SNP approach, rs9914220 and 22 additional SOCS3 SNPs were genotyped for genetic association analysis with measures of adiposity and glucose homeostasis. The adiposity phenotypes utilized in association analyses included BMI, WAIST, waist to hip ratio (WHR), subcutaneous adipose tissue, VAT, and visceral to subcutaneous ratio (VSR). Linkage disequilibrium calculations revealed three haplotype blocks near SOCS3. Haplotype Block 3 (5' of SOCS3) contained SNPs consistently associated with BMI, WAIST, WHR, and VAT (P-values ranging from 2.00 x 10(-4) to 0.036). Haplotype Block 1 contained single-SNPs that were associated with most adiposity traits except for VSR (P-values ranging from 0.002 to 0.047). When trait associated SNPs were included in linkage analyses as covariates, a reduction of VAT LOD score from 1.26 to 0.76 above the SOCS3 locus (110 cM) was observed. Multi-SNP haplotype testing using the quantitative pedigree disequilibrium test was broadly consistent with the single-SNP associations. In conclusion, these results support a role for SOCS3 genetic variants in human obesity.

Dataset Information

Polymorphisms in the SOCS7 gene and glucose homeostasis traits.

Publications

Polymorphisms in the SOCS7 gene and glucose homeostasis traits.

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